Process for the preparation of organic bromides

ABSTRACT

The present invention provides a process for the preparation of organic bromides, by a radical bromodecarboxylation of carboxylic acids with a bromoisocyanurate.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a National Phase Application of PCT International Application No. PCT/IL2016/051083, International Filing Date Oct. 6, 2016, claiming priority of U.S. Provisional Patent Application No. 62/238,197, filed Oct. 7, 2015, which are hereby incorporated by reference.

FIELD OF THE INVENTION

The present invention provides a process for the preparation of organic bromides, by a radical bromodecarboxylation of carboxylic acids with a bromoisocyanurate. The invention further provides a radiation sensitive composition comprising a carboxylic acid and bromoisocyanurate which generates organic bromide upon electromagnetic irradiation.

BACKGROUND OF THE INVENTION

Organic bromides are stable organic compounds, which are used commercially for many applications, such as pharmaceuticals, agriculture, disinfectants, flame extinguishing agents, and dyes. Organic bromides have found wide use in numerous industrial applications as chemical intermediates for the production of other commercial organic compounds (Ullmann's Encyclopedia of Industrial Chemistry 2012, v. 6, 331-358; v. 8, 483-519).

Reaction of benzoic acid with tribromoisocyanuric acid (TBCA) in trifluoroacetic acid gave only 3-bromobenzoic acid—the product of electrophilic bromination of aromatic C—H bond (Synlett 2013 v. 24, 603-605).

Organic carboxylic acids are widely available and cheap raw materials in organic synthesis. Therefore, the oxidative decarboxylation of organic carboxylic acids with concomitant replacement by bromine (bromodecarboxylation) is an extremely useful method for regioselective synthesis of organic bromides.

The Hunsdiecker reaction (Tetrahedron 1971, v. 27, 5323) is a bromodecarboxylation reaction, which utilizes the treatment of anhydrous silver salt of organic acid with molecular bromine in an inert solvent. This reaction, however, is extremely sensitive to presence of trace amounts of water, which lead to the recovery of unreacted acid. Another way to perform the Hunsdiecker reaction is by using a mixture of organic carboxylic acid and Br₂/HgO (J. Org. Chem. 1965, v. 30, 415) instead of the silver salt.

Accordingly, the Hunsdiecker reaction and/or its modifications use heavy metal salts such as those of silver and mercury, therefore the disadvantages of such procedures for the pharmaceutical industry are obvious.

The Barton halo-de-carboxylation procedure (Barton et al., Tetrahedron 1985, v. 41, 3901; 1987, v. 43, 4321) is directed to the conversion of organic carboxylic acids to the esters of N-hydroxypyridine-2-thione. The thiohydroxamic esters are brominated by BrCCl₃. Thiopyridines are formed in the reaction as co-products.

Additional process for converting organic carboxylic acids to their corresponding bromides is by treating the carboxylic acid with (diacetoxyiodo)benzene and bromine or LiBr as bromine source (Tetrahedron 2000, v. 56, 2703; Synlett 2011, 1563). However, in this reaction, it is difficult to separate the desired product from iodobenzene, which is formed as co-product in the reaction.

A bromodecarboxylation of aromatic carboxylic acids using CuBr₂ as the halogen sources has been developed by Wu et. al. (Tetrahedron Letters 2010, v. 51, 6646) and Liu et. al. (Tetrahedron Letters 2013, v. 54, 3079), which also utilize the use of heavy metals in their reactions.

Another example for bromodecarboxylation utilizes the reagent system 1205-KBr for bromodecarboxylation of electron-rich arenecarboxylic acids (Synlett 2014, v. 25, 2508). This method, however, is limited to preparation of specific brominated phenol ether derivatives.

N-Bromoamides such as N-bromosuccinimide (Chem. Pharm. Bull. 2002, v. 50, 941), 1,3-dibromo-5,5-dimethylhydantoin (Bioorg. Med. Chem. 2008, v. 16, 10001; Bioorg. Med. Chem. Lett. 2011, v. 21, 3227; Tetrahedron 2014, v. 70, 318), dibromoisocyanuric acid (Monatsh. Chem. 1968, v. 99, 815; 1969, v. 100, 42 & 1977, v. 108, 1067), tribromoisocyanuric acid (Synlett 2013, v. 24, 603), are useful reagents for the electrophilic bromination of aromatic carboxylic acids in the meta-position with respect to the carboxylic group. However, the use of these reagents in bromo-decarboxylation reactions is rather limited.

For example, reaction of N-bromosuccinimide with arenecarboxylic acids, predominantly electron-rich arenecarboxylic acids, yields bromoarenes (IN803DEL1999; JOC 2009, v. 74, 8874; Tetrahedron Lett. 2007, v. 48, 5429). Reaction of 3-aryl acrylic and propiolic acids with N-bromosuccinimides (J. Org. Chem. 2002, v. 67, 7861) and tribromoisocyanuric acid (J. Braz. Chem. Soc. 2013, v. 24, 213) yields 2-bromovinyl and 2-bromoethynyl arenes. All of these reactions are heterolytic reactions that do not require initiation with radical initiators or UV-visible light irradiation.

The conversion of carboxylic acid R—CO₂H, to their corresponding bromide, R—Br, is therefore a rather difficult transformation. There is a need for the development of new strategies for bromodecarboxylation.

SUMMARY OF THE INVENTION

In one embodiment, this invention is directed to a process for the preparation of organic bromide of formula (1A) from a carboxylic acid of formula (2A) represented by scheme 1:

said process comprises radical bromodecarboxylation reaction of carboxylic acid (2A) with a bromoisocyanurate to yield organic bromide (1A); wherein said bromoisocyanurate is tribromoisocyanuric acid, dibromoisocyanuric acid, bromodichloroisocyanuric acid, dibromochloroisocyanuric acid, bromochloroisocyanuric acid, or any combination thereof; A is arene, alkane, cycloalkane or saturated heterocycle; n is an integer of at least 1; m is an integer of at least 0; and each Q is independently F, Cl, Br, R¹, acyl, C(O)R¹, C(O)OR¹, C(O)OMe, C(O)Cl, C(O)N(R¹)₂, CN, SO₂R¹, SO₃R¹, NO₂, N(R¹)₃ ⁺, OR¹, OCF₃, O-acyl, OC(O)R¹, OSO₂R¹, SR¹, S-acyl, SC(O)R¹, N(R¹)acyl, N(R¹)C(O)R¹, N(R¹)SO₂R¹, N(acyl)₂, N[C(O)R¹]SO₂R¹, N[C(O)R¹]₂, CF₃; or any two vicinal Q substituents are joined to form a 5- or 6-membered substituted or unsubstituted, saturated or unsaturated carbocyclic or heterocyclic ring;

wherein each R¹ is independently aryl, alkyl, cycloalkyl or heterocyclyl, wherein said R¹ is optionally substituted by one or more substituents of R²;

wherein each R² is independently F, Cl, Br, COOH, acyl, aryl, alkyl, cycloalkyl or heterocyclyl;

wherein if either one of R² in (2A) is carboxylic group COOH, then the respective R² in (1A) is Br;

wherein the position of said Br and Q in said structure of formula (1A) correspond to the same position of said COOH and Q, respectively in said structure of formula (2A).

In one embodiment, this invention is directed to a process for the preparation of bromoarene (1B)

from an arenecarboxylic acid (2B),

wherein said process comprises radical bromodecarboxylation reaction of carboxylic acid (2B) with a bromoisocyanurate; wherein Q¹, Q², Q³, Q⁴, and Q⁵, are each independently selected from: H, F, Cl, Br, R¹, COOH, acyl, C(O)R¹, C(O)OR¹, C(O)OMe, C(O)Cl, C(O)N(R¹)₂, CN, SO₂R¹, SO₃R¹, NO₂, N(R¹)₃ ⁺, OR¹, OCF₃, O-acyl, OC(O)R¹, OSO₂R¹, SR¹, S-acyl, SC(O)R¹, N(R¹)acyl, N(R¹)C(O)R², N(R¹)SO₂R¹, N(acyl)₂, N[C(O)R¹]SO₂R¹, N[C(O)R¹]₂, CF₃; or any two of Q¹ and Q², Q² and Q³, Q³ and Q⁴, or Q⁴ and Q⁵, are joined to form a 5- or 6-membered substituted or unsubstituted, saturated or unsaturated carbocyclic or heterocyclic ring;

wherein each R¹ is independently aryl, alkyl, cycloalkyl or heterocyclyl; wherein R¹ is optionally substituted by one or more substituents of R²;

wherein each R² is independently F, Cl, Br, COOH, acyl, aryl, alkyl, cycloalkyl or heterocyclyl;

wherein if either one of Q¹, Q², Q³, Q⁴, Q⁵, and/or R² in (2B) is carboxylic group COOH, then the respective Q¹, Q², Q³, Q⁴, Q⁵, and/or R² in (1B) is Br.

In one embodiment, this invention is directed to a radiation-sensitive composition comprising carboxylic acid of formula (2A)

and bromoisocyanurate which generates organic bromide of formula (1A)

upon electromagnetic irradiation, wherein the bromoisocyanurate is tribromoisocyanuric acid, dibromoisocyanuric acid, bromodichloroisocyanuric acid, dibromochloroisocyanuric acid, bromochloroisocyanuric acid, or any combination thereof; A is arene, alkane, cycloalkane or saturated heterocycle; n is an integer of at least 1; m is an integer of at least 0; each Q is independently F, Cl, Br, R¹, acyl, C(O)R¹, C(O)OR¹, C(O)Cl, C(O)N(R¹)₂, CN, SO₂R¹, SO₃R¹, NO₂, N(R¹)₃ ⁺, OR¹, OCF₃, O-acyl, OC(O)R¹, OSO₂R¹, SR¹, S-acyl, SC(O)R¹, N(R¹)acyl, N(R¹)C(O)R¹, N(R¹)SO₂R¹, N(acyl)₂, N[C(O)R¹]SO₂R¹, N[C(O)R¹]₂, CF₃; or any two vicinal Q substituents are joined to form a 5- or 6-membered substituted or unsubstituted, saturated or unsaturated carbocyclic or heterocyclic ring;

wherein each R¹ is independently aryl, alkyl, cycloalkyl or heterocyclyl, wherein R¹ is optionally substituted by one or more substituents of R²;

wherein each R² is independently F, Cl, Br, COOH, acyl, aryl, alkyl, cycloalkyl or heterocyclyl;

wherein if either one of R² in (2A) is a carboxylic group COOH, then the respective R² in (1A) is Br;

wherein the position of said Br and Q in said structure of formula (1A) correspond to the same position of said COOH and Q, respectively in said structure of formula (2A).

In one embodiment, this invention is directed to a composition comprising an organic bromide of formula (1A) or (1B)

wherein said organic bromide of formula (1A) or (1B) is prepared according to the process of this invention.

In one embodiment, the process and composition of this invention further comprises an additive. In another embodiment, said additive is Br₂ (bromine), a salt comprising bromide or a polybromide anion and an organic or inorganic cation; or any combination thereof.

In one embodiment, the process of the invention is conducted in the presence of an organic or an inorganic solvent or combination thereof and the composition of this invention comprises an organic or inorganic solvent or combination thereof. In another embodiment, the inorganic solvent is CO₂ or SO₂, or combination thereof. In another embodiment, the organic solvent is CH₃CN, CH₃NO₂, an ester, a hydrocarbon solvent, or halocarbon solvent or combination thereof. In another embodiment, the hydrocarbon solvent is C₆H₆. In another embodiment, the halocarbon solvent is CH₂Cl₂, Cl(CH₂)₂Cl, CHCl₃, CCl₄, C₆H₅Cl, o-C₆H₄Cl₂, BrCCl₃, CH₂Br₂, CFCl₃, CF₃CCl₃, ClCF₂CFCl₂, BrCF₂CFClBr, CF₃CClBr₂, CF₃CHBrCl, C₆H₅F, C₆H₅CF₃, 4-ClC₆H₄CF₃, 2,4-Cl₂C₆H₃CF₃ or any combination thereof.

In one embodiment, in order to accelerate the radical bromodecarboxylation reaction the reaction mixture is subjected to electromagnetic irradiation. In another embodiment, the electromagnetic irradiation is microwave, infrared, ultraviolet, or visible light irradiation or any combination thereof. In another embodiment, the electromagnetic irradiation is visible light irradiation. In another embodiment, the source of said visible light is sunlight, fluorescent lamp, light-emitting diode, incandescent lamp or any combination thereof.

In one embodiment, the process and composition of this invention comprises bromoisocyanurate and a carboxylic acid compound of formula (2A) or (2B). In another embodiment, the molar ratio between bromoisocyanurate/(each carboxylic group of the carboxylic acid of formula (2A)) is between 0.1 and 2.

In one embodiment, the process and composition of this invention comprises bromoisocyanurate, additive and a carboxylic acid compound of formula (2A) or (2B). In another embodiment, the molar ratio between the additive/(each carboxylic group of the carboxylic acid of formula (2A)) is between 0.1 and 4.

In one embodiment, the bromodecarboxylation reaction is conducted at a temperature of between −20° C. and 150° C. In another embodiment, the bromodecarboxylation reaction is conducted at a temperature of between 0° C. and 100° C.

DETAILED DESCRIPTION OF THE PRESENT INVENTION

In the following detailed description, numerous specific details are set forth in order to provide a thorough understanding of the invention. However, it will be understood by those skilled in the art that the present invention may be practiced without these specific details. In other instances, well-known methods, procedures, and components have not been described in detail so as not to obscure the present invention.

In recent years, free radical reactions have developed greatly in the general field of organic synthesis. These free radical reactions have a number of significant advantages relative to the more conventional ionic reactions. First, free radical chain reactions can generally be conducted under neutral conditions. In addition, these reactions are performed under very mild conditions, which make it possible to avoid interference of a steric or polar nature occurring with the starting materials. Furthermore, this type of reaction is generally not accompanied by spurious reactions of carbocationic rearrangement or carbanionic elimination.

The present invention therefore had the object of perfecting a new process for the formation of carbon containing free radicals, the functionality of which is unmodified relative to the starting materials. The process of the invention consists essentially of a free radical bromodecarboxylation of organic acids which can be aromatic or aliphatic carboxylic acid. The mild conditions for carrying out this process have enabled excellent yields of free radicals to be obtained which retain, in particular, the ether, ester, ketone, and nitro functions of the starting material.

In one embodiment, this invention is directed to a process for the preparation of organic bromide of formula (1A) from a carboxylic acid of formula (2A) represented by scheme 1:

said process comprises radical bromodecarboxylation reaction of carboxylic acid (2A) with a bromoisocyanurate to yield organic bromide (1A); wherein said bromoisocyanurate is tribromoisocyanuric acid, dibromoisocyanuric acid, bromodichloroisocyanuric acid, dibromochloroisocyanuric acid, bromochloroisocyanuric acid, or any combination thereof; A is arene, alkane, cycloalkane or saturated heterocycle; n is an integer of at least 1; m is an integer of at least 0; and each Q is independently F, Cl, Br, R¹, acyl, C(O)R¹, C(O)OR¹, C(O)Cl, C(O)N(R¹)₂, CN, SO₂R¹, SO₃R¹, NO₂, N(R¹)₃ ⁺, OR¹, OCF₃, O-acyl, OC(O)R¹, OSO₂R¹, SR¹, S-acyl, SC(O)R¹, N(R¹)acyl, N(R¹)C(O)R¹, N(R¹)SO₂R¹, N(acyl)₂, N[C(O)R¹]SO₂R¹, N[C(O)R¹]₂, CF₃; or any two vicinal Q substituents are joined to form a 5- or 6-membered substituted or unsubstituted, saturated or unsaturated carbocyclic or heterocyclic ring;

wherein each R¹ is independently aryl, alkyl, cycloalkyl or heterocyclyl, wherein said R¹ is optionally substituted by one or more substituents of R²;

wherein each R² is independently F, Cl, Br, COOH, acyl, aryl, alkyl, cycloalkyl or heterocyclyl;

wherein if either one of R² in (2A) is carboxylic group COOH, then the respective R² in (1A) is Br;

wherein the position of said Br and Q in said structure of formula (1A) correspond to the same position of said COOH and Q, respectively in said structure of formula (2A).

In one embodiment, this invention is directed to a process for the preparation of organic bromide of formula (1B) from a carboxylic acid of formula (2B) represented by scheme 2:

said process comprises radical bromodecarboxylation reaction of carboxylic acid (2B) with a bromoisocyanurate to yield organic bromide (1B); wherein said bromoisocyanurate is tribromoisocyanuric acid, dibromoisocyanuric acid, bromodichloroisocyanuric acid, dibromochloroisocyanuric acid, bromochloroisocyanuric acid, or any combination thereof; wherein Q¹, Q², Q³, Q⁴, and Q⁵, are each independently selected from: H, F, Cl, Br, COOH, R¹, acyl, C(O)R¹, C(O)OR¹, C(O)Cl, C(O)N(R¹)₂, CN, SO₂R¹, SO₃R¹, NO₂, N(R¹)₃ ⁺, OR¹, OCF₃, O-acyl, OC(O)R¹, OSO₂R¹, SR¹, S-acyl, SC(O)R¹, N(R¹)acyl, N(R¹)C(O)R², N(R¹)SO₂R¹, N(acyl)₂, N[C(O)R¹]SO₂R¹, N[C(O)R¹]₂, CF₃; or any two of Q¹ and Q², Q² and Q³, Q³ and Q⁴, or Q⁴ and Q⁵, are joined to form a 5- or 6-membered substituted or unsubstituted, saturated or unsaturated carbocyclic or heterocyclic ring;

wherein each R¹ is independently aryl, alkyl, cycloalkyl or heterocyclyl; wherein R¹ is optionally substituted by one or more substituents of R²;

wherein each R² is independently F, Cl, Br, COOH, acyl, aryl, alkyl, cycloalkyl or heterocyclyl;

wherein if either one of Q¹, Q², Q³, Q⁴, Q⁵, and/or R² in (2B) is carboxylic group COOH, then the respective Q¹, Q², Q³, Q⁴, Q⁵, and/or R² in (1B) is Br.

In one embodiment, A of the organic bromide (1A) and of the carboxylic acid (2A) in scheme 1 is arene. In another embodiment, A of the organic bromide (1A) and the carboxylic acid (2A) in scheme 1 is an alkane. In another embodiment, A of the organic bromide (1A) and of the carboxylic acid (2A) in scheme 1 is a cycloalkane. In another embodiment, A of the organic bromide (1A) and of the carboxylic acid (2A) in scheme 1 is a saturated heterocycle.

In one embodiment the A is substituted with one or more substituents Q (in Scheme 1); where each Q is independently F, Cl, Br, R¹, acyl, C(O)R¹, C(O)OR¹, C(O)Cl, C(O)N(R¹)₂, CN, SO₂R¹, SO₃R¹, NO₂, N(R¹)₃ ⁺, OR¹, OCF₃, O-acyl, OC(O)R¹, OSO₂R¹, SR¹, S-acyl, SC(O)R¹, N(R¹)acyl, N(R¹)C(O)R¹, N(R¹)SO₂R¹, N(acyl)₂, N[C(O)R¹]SO₂R¹, N[C(O)R¹]₂, CF₃; or any two vicinal Q substituents are joined to form a 5- or 6-membered substituted or unsubstituted, saturated or unsaturated carbocyclic or heterocyclic ring;

wherein each R¹ is independently aryl, alkyl, cycloalkyl or heterocyclyl, wherein R¹ is optionally substituted by one or more substituents of R²;

wherein each R² is independently F, Cl, Br, COOH, acyl, aryl, alkyl, cycloalkyl or heterocyclyl.

In another embodiment, Q does not comprise electron donating substituents in the aromatic ring. Examples for electron donating substitutions include but not limited to: OH, NH₂, NH-alkyl, N(alkyl)₂.

In another embodiment, Q is at least one of NO₂, Cl, F, Br, CN, C(O)OMe, or CF₃.

In another embodiment, each Q is independently Cl. In another embodiment, each Q is independently F. In another embodiment, each Q is independently Br. In another embodiment, each Q is independently CN. In another embodiment, each Q is independently CF₃. In another embodiment, each Q is independently CCl₃. In another embodiment, each Q is independently acyl group. In another embodiment, each Q is independently SO₃R¹. In another embodiment, each Q is independently SO₂R¹. In another embodiment, each Q is independently COR¹. In another embodiment, each Q is independently C(O)OR¹. In another embodiment, each Q is independently C(O)OMe. In another embodiment, each Q is independently COCl. In another embodiment, each Q is independently amide. In another embodiment, each Q is independently C(O)N(R¹)₂. In another embodiment, each Q is independently OCF₃. In another embodiment, each Q is independently R¹. In another embodiment, each Q is independently alkyl. In another embodiment, each Q is independently t-Bu. In another embodiment, each Q is independently cycloalkyl. In another embodiment, each Q is independently heterocyclyl. In another embodiment, each Q is independently OR¹. In another embodiment, each Q is independently OMe. In another embodiment, each Q is independently SR¹. In another embodiment, each Q is independently SMe. In another embodiment, each Q is independently acetyl. In another embodiment, each Q is independently benzoyl. In another embodiment, each Q is independently mesyl. In another embodiment, each Q is independently tosyl. In another embodiment, each Q is independently NO₂. In another embodiment, each Q is independently N(R¹)₃ ⁺. In another embodiment, each Q is independently O-acyl. In another embodiment, each Q is independently OC(O)R¹. In another embodiment, each Q is independently acetoxy. In another embodiment, each Q is independently OSO₂R¹. In another embodiment, each Q is independently mesyloxy. In another embodiment, each Q is independently tosyloxy. In another embodiment, each Q is independently S-acyl. In another embodiment, each Q is independently SC(O)R¹. In another embodiment, each Q is independently N(R¹)acyl. In another embodiment, each Q is independently N(R¹)C(O)R¹. In another embodiment, each Q is independently N(R¹)SO₂R¹. In another embodiment, each Q is independently N(acyl)₂. In another embodiment, each Q is independently N[C(O)R¹]SO₂R¹. In another embodiment, each Q is independently saccharinyl. In another embodiment, each Q is independently N[C(O)R¹]₂. In another embodiment, each Q is independently phthalimido. In another embodiment, each Q is independently aryl. In another embodiment, each Q is independently C₆H₅. In another embodiment, each Q is independently C₆F₅. In another embodiment, two vicinal Q substituents are joined to form a 5- or 6-membered substituted or unsubstituted, saturated or unsaturated heterocyclic ring. In another embodiment, two vicinal Q substituents are joined to form dihydrofuran-2,5-dione. In another embodiment, two vicinal Q substituents are joined to form pyrrolidine-2,5-dione. In another embodiment, if m>1 then Q substituents are the same. In another embodiment, if m>1 then Q substituents are different.

In one embodiment, A of the organic bromide (1A) and of the carboxylic acid (2A) in scheme 1 is a benzene. In another embodiment, A is cycloalkane. In another embodiment, A is a saturated heterocycle.

In another embodiment A of the organic bromide (1A) and of the carboxylic acid (2A) in scheme 1 is an alkane. In another embodiment, the alkane chain is linear. In another embodiment, the alkane chain is branched.

In one embodiment, the carboxylic acid (2A) in scheme 1 is not ECH(Z)—COOH, wherein E is acyl, CO₂Z′, SO₂Z′, S(Z′)₂ ⁺, or N(Z′)₃+ and Z and Z′ are each independently a hydrogen, alkyl or an aryl. In another embodiment, the carboxylic acid (2A) in scheme 1 is not ZCH═CH—COOH or ZC≡C—COOH, where Z is either a hydrogen, alkyl or an aryl, the latter two are optionally substituted. In another embodiment, the A in scheme 1 is not unsaturated heterocycle. In another embodiment, the A in scheme 1 is not alkene or alkyne. In another embodiment, the A in scheme 1 is not cycloalkene or cycloalkyne. In another embodiment, the Q in scheme 1 is not OH, NH₂, NHR, or NR₂ group.

In another embodiment, at least one of Q¹, Q², Q³, Q⁴, and/or Q⁵ is F, Cl, Br, CF₃, CCl₃, CN, COOH, C(O)OMe, NO₂, phthalimide, OCF₃, and/or any two of Q¹ and Q², Q² and Q³, Q³ and Q⁴, or Q⁴ and Q⁵, are joined to form a dihydrofuran-2,5-dione or pyrrolidine-2,5-dione ring.

In another embodiment, at least one of Q¹, Q², Q³, Q⁴, and Q⁵ is NO₂. In another embodiment, at least one of Q¹, Q², Q³, Q⁴, and Q⁵ is CF₃. In another embodiment, at least one of Q¹, Q², Q³, Q⁴, and Q⁵ is CN. In another embodiment, at least one of Q¹, Q², Q³, Q⁴, and Q⁵ is Cl. In another embodiment, at least one of Q¹, Q², Q³, Q⁴, and Q⁵ is F. In another embodiment, at least one of Q¹, Q², Q³, Q⁴, and Q⁵ is Br. In another embodiment, at least one of Q¹, Q², Q³, Q⁴, and Q⁵ is phthalimide. In another embodiment, at least one of Q¹, Q², Q³, Q⁴, and Q⁵ is C(O)OMe.

In one embodiment, Q¹ of formula (1B) and (2B) in scheme 2 is F. In another embodiment, Q¹ is H. In another embodiment, Q¹ is CF₃. In another embodiment, Q¹ is Cl. In another embodiment, Q¹ is Br. In another embodiment, Q¹ is NO₂. In another embodiment, Q¹ is CO₂Me. In another embodiment, Q¹ is phthalimide.

In one embodiment, Q² of formula (1B) and (2B) in scheme 2 is H. In another embodiment, Q² is F. In another embodiment, Q² is CF₃. In another embodiment, Q² is Cl. In another embodiment, Q² is Br. In another embodiment, Q² is CN. In another embodiment, Q² is NO₂. In another embodiment, Q² is CO₂Me. In another embodiment, Q² is COOH.

In one embodiment, Q³ of formula (1B) and (2B) in scheme 2 is H. In another embodiment, Q³ is CN. In another embodiment, Q³ is Cl. In another embodiment, Q³ is Br. In another embodiment, Q³ is F. In another embodiment, Q³ is CF₃. In another embodiment, Q³ is NO₂. In another embodiment, Q³ is CO₂Me. In another embodiment, Q³ is COOH.

In one embodiment, Q⁴ of formula (1B) and (2B) in scheme 2 is H. In another embodiment, Q⁴ is F. In another embodiment, Q⁴ is CF₃. In another embodiment, Q⁴ is CN. In another embodiment, Q⁴ is Cl. In another embodiment, Q⁴ is NO₂.

In one embodiment, Q⁵ of formula (1B) and (2B) in scheme 2 is H. In another embodiment, Q⁵ is F. In another embodiment, Q⁵ is CF₃. In another embodiment, Q⁵ is CN. In another embodiment, Q⁵ is Cl.

In one embodiment, Q³ and Q⁴ of formula (1B) and (2B) in scheme 2 are joined to form a 5- or 6-membered substituted or unsubstituted, saturated or unsaturated heterocyclic ring. In another embodiment, the heterocyclic ring is dihydrofuran-2,5-dione. In another embodiment, the heterocyclic ring is pyrrolidine-2,5-dione. In another embodiment, the heterocyclic ring is substituted with an alkyl. In another embodiment, the alkyl is t-Bu.

In one embodiment, m of scheme 1 and of compounds (1A) and (2A) is an integer number greater than or equal to 0. In another embodiment, m is 0. In another embodiment, m is 1. In another embodiment, m is 2. In another embodiment, m is 3. In another embodiment, if m>1 than Q can be different or the same.

In one embodiment, n of compounds (1A), (2A) in scheme 1 is an integer number greater than or equal to 1. In another embodiment, n is between 1 and 5. In another embodiment, n is between 1 and 3. In another embodiment, n is 1 or 2. In another embodiment, n is 1. In another embodiment, n is 2. In another embodiment, n is 3.

In one embodiment, this invention is directed to a process for the preparation of organic bromide from its corresponding carboxylic acid, said process comprises a radical bromodecarboxylation reaction of the carboxylic acid with a bromoisocyanurate, wherein said carboxylic acid is selected from the carboxylic acids listed in Tables 4, 5, 6 and 11 below.

According to this invention, the term “bromoisocyanurate” refers to tribromoisocyanuric acid, dibromoisocyanuric acid, bromodichloroisocyanuric acid, dibromochloroisocyanuric acid, bromochloroisocyanuric acid, or any combination thereof. In one embodiment, the bromoisocyanurate reagent used in the process of the invention is freshly prepared according to known procedures [Journal of the Swimming Pool and Spa Industry 2004, v. 5, 16]. In another embodiment, tribromoisocyanuric acid, dibromoisocyanuric acid, bromodichloroisocyanuric acid, dibromochloroisocyanuric acid, and/or bromochloroisocyanuric acid are stable. In another embodiment, dibromoisocyanuric acid is commercially available.

In one embodiment, the process of this invention, represented by schemes 1 and 2, has a radical mechanism. In another embodiment all factors that promote radical reaction may stimulate the process of this invention. Factors that promote radical reaction: heating, electromagnetic irradiation, addition of radical initiators

In one embodiment, the reaction mixture of the process of this invention and the composition of this invention further comprises an additive. In another embodiment, the additive is bromine, a salt comprising bromide or a polybromide anion and an organic or inorganic cation; or any combination thereof. In another embodiment, the cation is a substituted or unsubstituted onium ion. The term “onium” refers in one embodiment to cations (with their counter-ions) derived by addition of a hydron to a mononuclear parent hydride of the nitrogen, chalcogen and halogen families. Non limiting examples of oniums include [NH₄]⁺ ammonium, [OH₃]⁺ oxonium, [PH₄]⁺ phosphonium, [SH₃]⁺ sulfonium, [AsH₄]⁺ arsonium, [SeH₃]⁺ selenonium, [BrH₂]⁺ bromonium, [SbH₄]⁺) stibonium, [TeH₃]⁺) telluronium, [IH₂]⁺ iodonium, [BiH₄]⁺ bismuthonium.

Substituted oniums refers to substitution of the above parent ions by univalent groups or by two or three free valencies. E.g. [SMe₃]⁺ trimethylsulfonium (a tertiary sulfonium ion), [MePPh₃]⁺ methyltriphethylphosphonium (a quaternary phosphonium ion), [HNEt₃]⁺ triethylammonium (a tertiary ammonium ion), [NPr₄]⁺ tetrapropylammonium (a quaternary ammonium ion), [R₂C═NR₂]⁺ iminium ions.

In one embodiment, the term “inorganic cation” used herein refers to alkali or alkaline earth metal cations, transition metal cation, or unsubstituted onium cation. In another embodiment, the inorganic cation is Li⁺. In another embodiment, the inorganic cation is Na⁺. In another embodiment, the inorganic cation is K⁺. In another embodiment, the inorganic cation is Rb⁺. In another embodiment, the inorganic cation is Cs⁺. In another embodiment, the inorganic cation is Zn²⁺. In another embodiment, the inorganic cation is Cu²⁺. In another embodiment, the inorganic cation is ammonium cation [Na₄]⁺.

In one embodiment, the term “organic cation” used herein refers to substituted onium cation. In another embodiment, the substituted onium cation is substituted ammonium cation, substituted phosphonium cation, substituted oxonium cation, substituted sulfonium cation, substituted arsonium cation, substituted selenonium cation, substituted telluronium cation, substituted iodonium cation, any other known onium cation, or any combination thereof. In another embodiment, the substituted ammonium cation is the substituted or unsubstituted guanidinium cation, substituted or unsubstituted pyridinium cation, substituted or unsubstituted amidinium cation, substituted or unsubstituted quaternary ammonium cation [NR¹ ₄]⁺, substituted or unsubstituted tertiary ammonium cation [HNR¹ ₃]⁺. In another embodiment, the substituted phosphonium cation is substituted or unsubstituted quaternary phosphonium cation [PR¹ ₄]⁺, wherein R¹ is alkyl, aryl, cycloalkyl, heterocyclyl, or any combination thereof. In another embodiment, the quaternary ammonium cation [NR¹ ₄]⁺ is tetraalkylammonium, trialkylarylammonium, dialkyldiarylammonium, trialkylbenzylammonium, or any combination thereof. In another embodiment, non-limiting examples of the quaternary ammonium cation [NR¹ ₄]⁺ include tetrametylammonium, tetraethylammonium, tetrabutylammonium, tetraoctylammonium, trimethyloctylammonium, cetyltrimethylammonium, or any combination thereof. In another embodiment, the quaternary phosphonium cation [PR¹ ₄]⁺ is tetraalkylphosphonium, alkyltriarylphosphonium, benzyltriarylphosphonium, benzyltrialkylphosphonium, or any combination thereof. In another embodiment, non-limiting examples of the quaternary phosphonium cation [PR¹ ₄]⁺ include tetraphenylphosphonium, benzyltriphenylphosphonium, tetrabutylphosphonium, methyltriphenylphosphonium, benzyltributylphosphonium cation or any combination thereof. In another embodiment, the substituted sulfonium cation is substituted or unsubstituted tertiary sulfonium cation, substituted or unsubstituted sulfoxonium, thiopyrylium or thiuronium ion; or any combination thereof. In another embodiment the substituted oxonium cation is substituted or unsubstituted tertiary oxonium cation, substituted or unsubstituted pyrylium cation; or any combination thereof.

In another embodiment, substituted cations as referred herein are substituted with halide, nitrile, nitro, alkyl, aryl, cycloalkyl, heterocyclyl, amide, carboxylic acid, acyl or any combination thereof.

In one embodiment, the term “polybromide anion” used herein refers to a molecule or ion containing three or more bromine atoms or to an ion of formula [Br_(p)]^(q−), where p is an integer of at least 3 and q is an integer of at least 1 and not more than p/2. In another embodiment, p is an integer between 3-24 and q is 1 or 2. In another embodiment p is 3, 5, 7, 9, 11 or 13 and q is 1. In another embodiment p is 4, 8, 20 or 24 and q is 2.

In another embodiment, the additive is Br₂, [NPr₄]Br, [NPr₄]Br₃, [NPr₄]Br₉, or any combination thereof.

An “alkyl” refers, in one embodiment, to a univalent groups derived from alkanes by removal of a hydrogen atom from any carbon atom: C_(n)H_(2n+1)—. In one embodiment, the alkyl group has 1-20 carbons. Examples for alkyls include but are not limited to: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, tert-butyl, pentyl, neopentyl, octyl, isooctyl and the like

The term “alkane” refers to acyclic branched or unbranched hydrocarbons having the general formula C_(n)H_(2n+2), and therefore consisting entirely of hydrogen atoms and saturated carbon atoms. Examples of alkane include: methane, ethane, propane, n-butane, isobutane, n-pentane, neopentane, n-octane, isooctane and the like.

An “arene” refers to monocyclic and polycyclic aromatic hydrocarbons. Nonlimiting examples of arenes are benzene, biphenyl, naphthalene, anthracene, and the like.

An “aryl” group refers, to univalent groups derived from arenes by removal of a hydrogen atom from a ring carbon atom. Nonlimiting examples of aryl groups are phenyl, naphthyl, antracenyl, phenanthryl, and the like.

A “cycloalkyl” refers to univalent groups derived from cycloalkanes by removal of a hydrogen atom from a ring carbon atom Non limiting examples of cycloalkyl include: cyclobutyl, norbornyl, cyclopentyl and cyclohexyl.

A “cycloalkane” refers to saturated mono- or polycyclic hydrocarbons. A general chemical formula for cycloalkanes would be C_(n)H_(2(n+1−g)) where n=number of C atoms and g=number of rings in the molecule.

A “heterocyclyl” refers to univalent groups formed by removing a hydrogen atom from any ring atom of a mono or polycyclic heterocyclic compound.

A “heterocycle” refers to a mono- or poly-cyclic heterocyclic compound consisting of carbon, hydrogen and at least one of nitrogen, sulfur, oxygen, phosphorous or combination thereof in one of the rings. In one embodiment, the heterocyclic compound consists 2-7 fused rings. Non limiting examples of monocyclic saturated heterocyclic compounds are aziridine, oxirane, thiirane, azetidine, oxetane, thietane, pyrrolidine, tetrahydrofurane, thiolane, pyperidine, oxane, thiane, azepane, oxepane, thiepane, imidazolidine, oxazolidine, thiazolidine, dioxolane, piperazine, morpholine, dioxane, homopiperazine. Non limiting examples of saturated bicyclic heterocyclic compounds are quinuclidine, 7-oxanorbornane, 7-thiabicyclo[2.2.1]heptane, 3-oxabicyclo[3.1.1]heptane, 3-azabicyclo[3.1.1]heptane, octahydroindole, octahydro-2-benzofuran.

An “amide” refers, in one embodiment, to a derivative of oxoacid in which an acidic hydroxyl group has been replaced by an amino or substituted amino group. Compounds having one or two acyl groups on a given nitrogen are generically included and may be designated as primary and secondary amides, respectively.

An “acyl” group is formed by removing one or more hydroxyl groups from oxoacids, and replacement analogues of such acyl groups. E.g. —C(═O)R, —C(═O)OR, —C(═O)NR₂, —C≡N, —S(═O)₂R, —S(═O)₂OR, —NO₂. Non limiting examples of the acyl groups include acetyl —C(O)Me, benzoyl —C(O)Ph, C(O)OMe, —C(═O)Cl, mesyl MeSO₂—, tosyl 4-MeC₆H₄SO₂—,

A “carboxylic acid” refers, in one embodiment, to oxoacids having the structure RC(═O)OH.

In another embodiment, the bromodecarboxylation reaction represented by schemes 1 and 2 is conducted at room temperature. In another embodiment, the reaction is conducted under cooling. In another embodiment, the bromodecarboxylation reaction is initiated thermally. In another embodiment, the bromodecarboxylation reaction is further subjected to heat. In another embodiment, the bromodecarboxylation reaction is conducted at a temperature of between −20° C. and 150° C. In another embodiment, said process is conducted at a temperature of between about 0° C. and about 100° C.

In another embodiment, the process of this invention further comprising the use of radical initiator in the reaction. In another embodiment, the radical initiator is an azo compound or organic peroxide. In another embodiment, the azo compound is azobisisobutyronitrile (AIBN) or 1,1′-azobis(cyclohexanecarbonitrile) (ABCN). In another embodiment, the organic peroxide is benzoyl peroxide.

In another embodiment, the bromoarene of formula (1A) and/or (1B) is prepared according to process described in Examples 3-11.

In one embodiment, the process of this invention, represented by schemes 1 and 2, is conducted under electromagnetic irradiation. In another embodiment, the electromagnetic radiation is visible light, infrared radiation, ultraviolet radiation, microwave radiation or any combination thereof.

In another embodiment, the source of the visible light is sunlight, fluorescent lamp, light-emitting diode, incandescent lamp or any combination thereof.

The term “irradiation” refers in one embodiment to the energy that is irradiated or transmitted in the form of rays or waves or particles. Electromagnetic irradiation refers to radiation consisting of waves of energy associated with electric and magnetic fields resulting from the acceleration of an electric charge. Ultrasound refers to cyclic mechanical vibrations with a frequency greater than 20 kilohertz (20,000 hertz). Ultraviolet irradiation refers to electromagnetic radiation with wavelengths 100 to 400 nm. Visible irradiation (light, visible light) refers to electromagnetic irradiation with wavelengths 400 to 780 nm. Infrared irradiation refers to electromagnetic irradiation with wavelengths 780 to 20000 nm. Microwave irradiation refers to electromagnetic irradiation with wavelengths 2 to 1000 mm.

Devices serving as a source of the electromagnetic irradiation include a mercury lamp, a xenon lamp, a carbon arc lamp, an incandescent lamp, a tungsten lamp, a fluorescent lamp, light-emitting diode, and sunlight, and the like.

Tungsten lamp refers to incandescent lamp that generates light by passing an electric current through a thin filament wire (usually of wolfram) until it is extremely hot. The lamps are often filled by a halogen gas such as iodine and bromine that allow filaments to work at higher temperatures and higher efficiencies.

Light-emitting diode (LED) refers to a semiconductor (often a combination of gallium, arsenic, and phosphorous or gallium and nitrogen) containing an n region (where electrons are more numerous than positive charges) separated from a p region (where positive charges are more numerous than negative charges). Upon application of a voltage, charges move and emission of ultraviolet, visible, or infrared radiation is produced each time a charge recombination takes place. Although an LED emits incoherent monochromatic light, normally a very narrow frequency range is obtained.

In another embodiment, the process is conducted in the presence of an organic or an inorganic solvent or combination thereof and the composition of this invention comprises an organic or an inorganic solvent or combination thereof. In another embodiment, the organic solvent is CH₃CN, CH₃NO₂, ester, a hydrocarbon solvent, or halocarbon solvent or combination thereof. In another embodiment the halocarbon solvent is CH₂Cl₂, Cl(CH₂)₂Cl, CHCl₃, CCl₄, C₆H₅Cl, o-C₆H₄Cl₂, BrCCl₃, CH₂Br₂, CFCl₃, CF₃CCl₃, ClCF₂CFCl₂, BrCF₂CFClBr, CF₃CClBr₂, CF₃CHBrCl, C₆H₅F, C₆H₅CF₃, 4-ClC₆H₄CF₃, 2,4-Cl₂C₆H₃CF₃ or any combination thereof. In another embodiment, the solvent is CH₂Cl₂ or BrCCl₃. In another embodiment, the solvent is a polar solvent. In another embodiment, the solvent is a nonpolar solvent. In another embodiment, the solvent is a hydrocarbon. In another embodiment, the solvent is benzene C₆H₆ (PhH). In another embodiment, the solvent is acetonitrile CH₃CN (MeCN). In another embodiment, the solvent is ethyl acetate EtOAc. In another embodiment, the solvent is halocarbon. In another embodiment, the solvent is carbon tetrachloride CCl₄. In another embodiment, the solvent is chloroform CHCl₃. In another embodiment, the solvent is bromotrichloromethane BrCCl₃. In another embodiment, the solvent is dibromomethane CH₂Br₂. In another embodiment, the solvent is trichlorofluoromethane CFCl₃. In another embodiment, the solvent is 1,1,1-trichlorotrifluoroethane CF₃CCl₃. In another embodiment, the solvent is 1,1,2-trichlorotrifluoroethane ClCF₂CFCl₂. In another embodiment, the solvent is 1,2-dibromo-1-chlorotrifluoroethane BrCF₂CFClBr. In another embodiment, the solvent is 1,1-dibromo-1-chlorotrifluoroethane CF₃CClBr₂. In another embodiment, the solvent is 2-bromo-2-chloro-1,1,1-trifluoroethane CF₃CHBrCl (halothane). In another embodiment, the solvent is fluorobenzene C₆H₅F (PhF). In another embodiment, the solvent is chlorobenzene C₆H₅Cl (PhCl). In another embodiment, the solvent is benzotrifluoride C₆H₅CF₃ (PhCF₃). In another embodiment, the solvent is p-chlorobenzotrifluoride 4-ClC₆H₄CF₃. In another embodiment, the solvent is 1,2-dichloroethane Cl(CH₂)₂Cl (DCE). In another embodiment, the solvent is ortho-dichlorobenzene o-C₆H₄Cl₂. In another embodiment, the solvent is dichloromethane CH₂Cl₂ (DCM). In another embodiment, the solvent is 2,4-dichlorobenzotrifluoride 2,4-Cl₂C₆H₃CF₃. In another embodiment, bromodecarboxylation process is preferably conducted in a halocarbon solvent. In another embodiment, bromodecarboxylation process is preferably conducted in a BrCCl₃, CH₂Cl₂, CH₂Br₂, CF₃CHBrCl or any combination thereof.

The term “hydrocarbon solvent” refers to any solvent consisting of the carbon and hydrogen elements. Non limiting examples of hydrocarbon solvents are cyclohexane, heptane, pentane, hexane, or benzene C₆H₆.

The term “halocarbon solvent” refers to any solvent wherein one or more of the carbons are covalently linked to one or more halogens (fluorine, chlorine, or bromine). Non limiting examples of halocarbon solvents are chloroform CHCl₃, dichloromethane CH₂Cl₂ (DCM), bromotrichloromethane BrCCl₃, chlorobenzene C₆H₅Cl (PhCl), ortho-dichlorobenzene o-C₆H₄Cl₂, 1,2-dichloroethane Cl(CH₂)₂Cl (DCE), carbon tetrachloride CCl₄, 1,3-dichloropropane Cl(CH₂)₃Cl, 1,1,2,2-tertrachlorodifluoroethane FCCl₂CCl₂F, 1,1,2-trichloroethane CHCl₂CH₂Cl, bromobenzene C₆H₅Br, 1,1,2-trichlorotrifluoroethane ClCF₂CFCl₂, dibromomethane CH₂Br₂, 2-bromo-2-chloro-1,1,1-trifluoroethane CF₃CHBrCl (halothane), 1,2-dibromoethane Br(CH₂)₂Br, benzotrifluoride C₆H₅CF₃ (PhCF₃), 2,4-dichlorobenzotrifluoride 2,4-Cl₂C₆H₃CF₃.

In one embodiment, following the formation of organic bromide, or the compound of formula (1A) or (1B) the organic bromide is isolated from the reaction mixture by filtration, washing, chromatography, crystallization or any combination thereof. In another embodiment the bromo compound is isolated from the reaction mixture by filtration followed by a washing step. In another embodiment the washing step comprises washing with an aqueous reducing agent followed by washing with an aqueous base. In another embodiment the washing step comprises washing with an aqueous base followed by washing with an aqueous reducing agent. In another embodiment, the washing step comprises washing with an aqueous reducing agent and a base.

In one embodiment the organic bromide is isolated from the reaction mixture by a washing step.

In another embodiment, the washing step comprises treating of the reaction mixture with reducing agent, wherein excess of the bromoisocyanurate is converted to cyanuric acid insoluble in non-polar organic solvents, and thereby can be removed from the organic phase. In another embodiment, an aqueous reducing agent refers to an aqueous solution comprising a reducing agent. Non limiting examples of reducing agents are Na₂SO₃, NaHSO₃, Na₂S₂O₃, NaBH₄/NaOH or combination thereof. In another embodiment the reducing agent is added at a concentration of between 1-10% w/w to the water to obtain an aqueous reducing agent solution.

In one embodiment, the process of this invention directed to bromodecarboxylation comprising a washing step with an aqueous reducing agent. In another embodiment, following the washing step a potassium iodide starch paper test is performed to identify traces of the bromoisocyanurate. “A potassium iodide starch paper test” (SPT) refers to a starch iodide test paper that has been wetted with aqueous acetic acid; 1:1; v/v]. In another embodiment, if the test is positive, an additional aqueous reducing agent is added to the reaction mixture.

In another embodiment the washing step comprises washing the product with a mild aqueous base wherein the unreacted carboxylic acid is removed from the organic phase by washing with an aqueous base. In another embodiment, the carboxylic acid is recovered by acidifying the aqueous phase. In another embodiment, an aqueous base refers to an aqueous solution comprising a base. Non limiting examples of a base is NaHCO₃, NaOH, Na₂CO₃, KOH, Na₂SO₃ or combination thereof. In another embodiment the base is added at a concentration of between 1-10% w/w to the water to obtain an aqueous base solution.

In another embodiment, the washing step with an aqueous reducing agent is conducted before the washing step with the aqueous base. In another embodiment, the washing step with the aqueous base is conducted before the washing step with the aqueous reducing agent. In another embodiment, the washing step comprises washing with an aqueous reducing agent and a base.

Such a combination of an aqueous reducing agent and a base includes Na₂SO₃ and NaBH₄/NaOH which are basic reducing agents that combine properties of reducing agent and a base.

In another embodiment, the washing steps of this invention are conducted using the organic solvent of the reaction mixture as the organic phase. In another embodiment, the washing step with the aqueous base and the washing step with the aqueous reducing agent are independently performed using a) the organic solvent of the reaction mixture, b) a mixture of organic solvents, or c) a different organic solvent, as the organic phase. Non limiting examples of organic solvents used as an organic phase in the washing step are hydrocarbon solvent, halocarbon solvent, or esters such as cyclohexane, heptane, hexane, pentane, benzene, toluene, chlorobenzene, 1,2-dichloroethane, carbon tetrachloride, 1,3-dichloropropane, 1,1,2,2-tertrachlorodifluoroethane, 1,1,2-trichloroethane, trichloroethylene, perchloroethylene, dichloromethane, chloroform, ethyl acetate or butyl acetate.

In one embodiment, following the washing step, the aqueous phase is treated with an acid or an aqueous acid solution to precipitate solid cyanuric acid.

In one embodiment, the organic bromide product of the bromodecarboxylation reaction is soluble in organic phase and not soluble in the aqueous phase. In another embodiment, the crude organic bromide is isolated from reaction mixture by standard organic solvent extractive work-up.

In one embodiment, removing the solvent from the organic phase gives the crude desired bromide product as the residue. In another embodiment, the residue is the pure desired bromide product. In another embodiment, the bromide is purified by crystallization, rectification or chromatography of the residue.

In another embodiment the isolation and purification further comprises a drying step. In another embodiment the purification further comprises chromatography.

In one embodiment, the process of this invention provides a process for the preparation of pure organic bromide.

In another embodiment, the “pure bromide” refers to 92% or more purity. In another embodiment, the “pure bromide” refers to about 95% or more purity. In another embodiment, the “pure bromide” refers to about 90% or more purity. In another embodiment, the “pure bromide” refers to about 85% or more purity. In another embodiment, the “pure bromide” refers to about 99% or more purity. In another embodiment, the “pure bromide” refers to about 98% or more purity. In another embodiment, the “pure bromide” refers to about 97% or more purity.

In one embodiment, this invention is directed to organic bromide compound represented by the formula (1A) or (1B) having purity of about 99% or more, prepared according to the process of this invention. In another embodiment, this invention is directed to organic bromide compound represented by the formula (1A) or (1B) having purity of about 98% or more prepared according to the process of this invention. In another embodiment, this invention is directed to organic bromide compound represented by the formula (1A) or (1B) having purity of about 90% or more, prepared according to the process of this invention. In another embodiment, this invention is directed to organic bromide compound represented by the formula (1A) or (1B) having purity of about 95% or more, prepared according to the process of this invention. In another embodiment, this invention is directed to organic bromide compound represented by the formula (1A) or (1B) having purity of about 85% or more, prepared according to the process of this invention. In another embodiment, this invention is directed to organic bromide compound represented by the formula (1A) or (1B) having purity of about 97% or more, prepared according to the process of this invention.

In one embodiment, the process of this invention, represented by schemes 1 and 2, provides a yield of 60% or more. In another embodiment, the process of this invention provides a yield of 70% or more. In another embodiment, the process of this invention provides a yield of 80% or more. In another embodiment, the process of this invention provides a yield of 85% or more. In another embodiment, the process of this invention provides a yield of 90% or more. In another embodiment, the process of this invention provides a yield of 95% or more.

In one embodiment, this invention is directed to a process comprising reacting carboxylic acid of formula (2A) or (2B) with bromoisocyanurate and an additive in a certain molar ratio. In another embodiment, the carboxylic acid compounds (2A) or (2B) can have more than one carboxylic acid groups.

In one embodiment the bromoisocyanurate: (each carboxylic group of the carboxylic acid of formula (2A)) molar ratio is between 0.1 and 2. In another embodiment the bromoisocyanurate: (each carboxylic group of the carboxylic acid of formula (2A)) molar ratio is between 1 and 2. In another embodiment the bromoisocyanurate: (each carboxylic group of the carboxylic acid of formula (2A)) molar ratio is between 0.1 and 1. In another embodiment the bromoisocyanurate: (each carboxylic group of the carboxylic acid of formula (2A)) molar ratio is 1. In another embodiment the bromoisocyanurate: (each carboxylic group of the carboxylic acid of formula (2A)) molar ratio is between 1 and 1.5.

In one embodiment, the reaction mixture of the process according to this invention, further comprises an additive. In another embodiment, the additive: (each carboxylic group of the carboxylic acid of formula (2A)) molar ration is between 0.1 and 4. In another embodiment, additive: (each carboxylic group of the carboxylic acid of formula (2A)) molar ration is between 1 and 4. In another embodiment, the additive: ((each carboxylic group of the carboxylic acid of formula (2A)) molar ration is between 0.1 and 2. In another embodiment, the additive: (each carboxylic group of the carboxylic acid of formula (2A)) molar ration is between 0.1 and 1. In another embodiment the additive: (each carboxylic group of the carboxylic acid of formula (2A)) molar ration is between 1 and 2. In another embodiment the additive: (each carboxylic group of the carboxylic acid of formula (2A)) molar ration is between 1 and 3.

In one embodiment, this invention is directed to a radiation-sensitive composition comprising carboxylic acid of formula (2A)

and bromoisocyanurate which generates organic bromide of formula (1A)

upon electromagnetic irradiation, wherein the bromoisocyanurate is tribromoisocyanuric acid, dibromoisocyanuric acid, bromodichloroisocyanuric acid, dibromochloroisocyanuric acid, bromochloroisocyanuric acid, or any combination thereof; A is arene, alkane, cycloalkane or saturated heterocycle; n is an integer of at least 1; m is an integer of at least 0; each Q is independently F, Cl, Br, R¹, acyl, C(O)R¹, C(O)OR¹, C(O)Cl, C(O)N(R¹)₂, CN, SO₂R¹, SO₃R¹, NO₂, N(R¹)₃ ⁺, OR¹, OCF₃, O-acyl, OC(O)R¹, OSO₂R¹, SR¹, S-acyl, SC(O)R¹, N(R¹)acyl, N(R¹)C(O)R¹, N(R¹)SO₂R¹, N(acyl)₂, N[C(O)R¹]SO₂R¹, N[C(O)R¹]₂, CF₃; or any two vicinal Q substituents are joined to form a 5- or 6-membered substituted or unsubstituted, saturated or unsaturated carbocyclic or heterocyclic ring;

wherein each R¹ is independently aryl, alkyl, cycloalkyl or heterocyclyl, wherein R¹ is optionally substituted by one or more substituents of R²;

wherein each R² is independently F, Cl, Br, COOH, acyl, aryl, alkyl, cycloalkyl or heterocyclyl;

wherein if either one of R² in (2A) is a carboxylic group COOH, then the respective R² in (1A) is Br;

wherein said position of Br and Q in said structure of formula (1A) correspond to the same position of said COOH and Q, respectively in said structure of formula (2A)

In another embodiment A of formula (1A) or (2A) is arene. In another embodiment A of formula (1A) or (2A) is an alkane. In another embodiment A of formula (1A) or (2A) is cycloalkane or saturated heterocycle.

In another embodiment, this invention is directed to a radiation-sensitive composition comprising a carboxylic acid and bromoisocyanurate; wherein said carboxylic acid is represented by the structure of compound (2B):

wherein Q¹, Q², Q³, Q⁴, and Q⁵, are each independently selected from: H, F, Cl, Br, COOH, R¹, acyl, C(O)R¹, C(O)OR¹, C(O)Cl, C(O)N(R¹)₂, CN, SO₂R¹, SO₃R¹, NO₂, N(R¹)₃ ⁺, OR¹, OCF₃, O-acyl, OC(O)R¹, OSO₂R¹, SR¹, S-acyl, SC(O)R¹, N(R¹)acyl, N(R¹)C(O)R², N(R¹)SO₂R¹, N(acyl)₂, N[C(O)R¹]SO₂R¹, N[C(O)R¹]₂, CF₃; or any two of Q¹ and Q², Q² and Q³, Q³ and Q⁴, or Q⁴ and Q⁵, are joined to form a 5- or 6-membered substituted or unsubstituted, saturated or unsaturated carbocyclic or heterocyclic ring;

wherein each R¹ is independently aryl, alkyl, cycloalkyl or heterocyclyl; wherein R¹ is optionally substituted by R²;

wherein each R² is independently F, Cl, Br, COOH, acyl, aryl, alkyl, cycloalkyl or heterocyclyl;

wherein if either one of Q¹, Q², Q³, Q⁴, Q⁵, and/or R² in (2B) is carboxylic group COOH, then the respective Q¹, Q², Q³, Q⁴, Q⁵, and/or R² in (1B) is Br.

In one embodiment, this invention is directed to a composition comprising an organic bromide of formula (1A):

wherein said organic bromide of formula (1A) is prepared by reacting a carboxylic acid of formula (2A)

and bromoisocyanurate by electromagnetic irradiation; wherein A is arene, alkane, cycloalkane or saturated heterocycle; n is an integer of at least 1; m is an integer of at least 0; each Q is independently F, Cl, Br, R¹, acyl, C(O)R¹, C(O)OR¹, C(O)Cl, C(O)N(R¹)₂, CN, SO₂R¹, SO₃R¹, NO₂, N(R¹)₃ ⁺, OR¹, OCF₃, O-acyl, OC(O)R¹, OSO₂R¹, SR¹, S-acyl, SC(O)R¹, N(R¹)acyl, N(R¹)C(O)R¹, N(R¹)SO₂R¹, N(acyl)₂, N[C(O)R¹]SO₂R¹, N[C(O)R¹]₂, CF₃; or any two vicinal Q substituents are joined to form a 5- or 6-membered substituted or unsubstituted, saturated or unsaturated carbocyclic or heterocyclic ring;

wherein each R¹ is independently aryl, alkyl, cycloalkyl or heterocyclyl, wherein R¹ is optionally substituted by one or more substituents of R²;

wherein each R² is independently F, Cl, Br, COOH, acyl, aryl, alkyl, cycloalkyl or heterocyclyl;

wherein if either one of R² in (2A) is a carboxylic group COOH, then the respective R² in (1A) is Br;

wherein said position of Br and Q in said structure of formula (1A) correspond to the same position of said COOH and Q, respectively in said structure of formula (2A)

In one embodiment, this invention is directed to a composition comprising an organic bromide of formula (1B):

wherein said organic bromide of formula (1B) is prepared by reacting a carboxylic acid of formula (2B)

and bromoisocyanurate by electromagnetic irradiation; wherein Q¹, Q², Q³, Q⁴, and Q⁵, are each independently selected from: H, F, Cl, Br, COOH, R¹, acyl, C(O)R¹, C(O)OR¹, C(O)Cl, C(O)N(R¹)₂, CN, SO₂R¹, SO₃R¹, NO₂, N(R¹)₃ ⁺, OR¹, OCF₃, O-acyl, OC(O)R¹, OSO₂R¹, SR¹, S-acyl, SC(O)R¹, N(R¹)acyl, N(R¹)C(O)R², N(R¹)SO₂R¹, N(acyl)₂, N[C(O)R¹]SO₂R¹, N[C(O)R¹]₂, CF₃; or any two of Q¹ and Q², Q² and Q³, Q³ and Q⁴, or Q⁴ and Q⁵, are joined to form a 5- or 6-membered substituted or unsubstituted, saturated or unsaturated carbocyclic or heterocyclic ring;

wherein each R¹ is independently aryl, alkyl, cycloalkyl or heterocyclyl; wherein R¹ is optionally substituted by R²;

wherein each R² is independently F, Cl, Br, COOH, acyl, aryl, alkyl, cycloalkyl or heterocyclyl;

wherein if either one of Q¹, Q², Q³, Q⁴, Q⁵, and/or R² in (2B) is carboxylic group COOH, then the respective Q¹, Q², Q³, Q⁴, Q⁵, and/or R² in (1B) is Br.

Mechanism of the Bromodecarboxylation Reaction of the Invention

Without bounding to any particular mechanism or theory, it is contemplated that the process according to this invention is described as follows:

-   -   i. Bromination of the carboxylic acid R—CO₂H (corresponds to         compounds of formula (2A) and (2B)) with the bromoisocyanurate         to give the corresponding acyl hypobromite, R—CO₂Br, according         to equation (1):

-   -   ii. Homolytic degradation of the acyl hypobromite, R—CO₂Br, to         give carbon-centered free radical R. according to equation (2):         R—CO₂Br→R.+CO₂+Br.  (2)     -   iii. R. pulls out a bromine atom from nearest bromine atom donor         to yield bromide R—Br according to equation (3):         R.+bromine atom donor→R—Br  (3)         wherein the bromine atom donor is selected from: bromine radical         Br. (equation (2)), additive (e.g. Br₂, bromide, polybromides),         or the halocarbon solvent (e.g., BrCCl₃, CF₃CHBrCl).

It should be noted that the suggested mechanism presented above, is only a rough scheme of the complex real processes.

One indication for the radical chain mechanism of the bromodecarboxylation reaction is by using a 2,2,6,6-tetramethyl-1-piperidinynyloxyl (TEMPO) carbon-centered radical scavenger as a mechanistic diagnostic tool. Addition of TEMPO as radical chain inhibitor to the initial reaction mixture of the bromodecarboxylation reaction, inhibits the reaction. Inhibition of the bromodecarboxylation reaction by addition of TEMPO indicates that the reaction has a radical chain mechanism.

According to the present invention, the carbon-centered free radicals R. are obtained by applying photochemical and/or thermal energy to a mixture of carboxylic acid R—CO₂H, bromoisocyanurate and, optionally an additive. The photochemical energy increases the rate of the reaction.

The following examples are presented in order to more fully illustrate the preferred embodiments of the invention. They should in no way, however, be construed as limiting the broad scope of the invention.

EXAMPLES Experimental Details

Reagents:

All reagents and solvents were purchased from Sigma-Aldrich, Alfa Aesar, Acros Organics, and TCI unless specified otherwise. 3,5,5-Trimethylhydantoin 3,5,5-TMH and 4,4-dimethyl-2-oxazolidinone DMO were prepared according to published procedure (WO2015068159 A2).

Techniques:

All reactions were performed under nitrogen atmosphere in non-flame dried glassware. Mounted nearby the reaction flask 3 W LED warm-white lamp was used for irradiation of the reaction mixture. Conversions were determined by ¹H NMR, and yields of isolated product refer to products with more than 95% purity by ¹H NMR. Flash column chromatography was performed employing 63-200 μm silica gel 60 according to standard techniques (J. Org. Chem. 1978, v. 43, 2923).

Analytical Methods:

GC analyses were performed on Shimadzu GC-2010 gas chromatograph with flame ionization detector (FID) using a 30 m×0.25 mm Quadrex capillary column with methyl 5% phenyl silicone stationary phase, 0.25 μm film thickness. For TLC analysis, Merck precoated TLC plates (silica gel 60 F-254 on glass plates, 0.25 mm) were used. NMR spectra were recorded on a Bruker AM-400 (¹H at 400 MHz, ¹³C at 100 MHz) instruments using CDCl₃ (unless otherwise stated) as a solvent. Data are reported as follows: chemical shift in ppm relative to internal TMS, multiplicity, coupling constant in Hz and integration. Compounds described in the literature were characterized by comparing their ¹H and/or ¹³C NMR spectra to the previously reported data. New compounds were further characterized by high-resolution mass spectra.

The following abbreviations are used:

1,5,5-TMH=1,5,5-trimethylhydantoin

1-BTMH=1-bromo-3,5,5-trimethylhydantoin

3,5,5-TMH=3,5,5-trimethylhydantoin

3-BTMH=3-bromo-1,5,5-trimethylhydantoin

ABCN=1,1′-azobis(cyclohexanecarbonitrile)

AIBN=azobisisobutyronitrile

Alk=alkyl

APCI=atmospheric pressure chemical ionization

Ar=arene

BDMO=3-bromo-4,4-dimethyl-2-oxazolidinone or 3-bromo-4,4-dimethyloxazolidin-2-one

BNPT=N-bromo-4-nitrophthalimide

BPT=N-bromophthalimide

BNPT=N-bromo-4-nitrophthalimide

CTAB=cetyltrimethylammonium bromide

d=doublet

DBDMH=1,3-dibromo-5,5-dimethylhydantoin

DBI=dibromoisocyanuric acid

DCE=1,2-dichloroethane

DCM=dichloromethane

DMO=4,4-dimethyl-2-oxazolidinone or 4,4-dimethyloxazolidin-2-one

FL=fluorescent room lighting

hv=visible light irradiation

HRMS=high resolution/accurate mass spectrometer

LED=light-emitting diode

LL=LED lamp irradiation

m=multiplet

MBCA=monobromoisocyanuric acid

MCCA=monochloroisocyanuric acid

N-bromoimide=bromoimide, wherein bromine atom is attached directly to nitrogen atom

NBS=N-bromosuccinimide

NBSac=N-bromosaccharine

NL=dark

NMR=nuclear magnetic resonance

ppm=part per million

rt=room temperature

s=singlet

SDS=sodium dodecyl sulfate

t=triplet

TL=tungsten lamp irradiation

TBCA=tribromoisocyanuric acid

TEMPO=2,2,6,6-tetramethyl-1-piperidinyloxy, free radical

Δ=heating

Example 1 Preparation of N-bromoamides

General Method A:

A mixture of amide (1.0 mmol), PhI(OAc)₂ (0.6 mmol), Br₂ (0.8 mmol), and MeCN (5-10 mL) was stirred at rt for 3-40 h and then concentrated in vacuo. CCl₄, cyclohexane, or benzene (5-10 mL) was added to the residue and the obtained mixture was stirred for 15 min at rt and 1 h at 0 to 5° C. The precipitated solid was filtered, washed on the filter with cold CCl₄, cyclohexane, or benzene and dried in vacuo to give the desired N-bromoimide as an off-white powder.

General Method B:

A mixture of amide (1.0 mmol), PhI(OAc)₂ (0.6 mmol), Br₂ (0.8 mmol), and CCl₄, benzene, or cyclohexane (5-10 mL) was stirred for 4-40 h at rt and for 1 h at 0 to 5° C. The precipitated solid was filtered, washed on the filter with cold CCl₄, benzene, or cyclohexane and dried in vacuo to give N-bromoimide as an off-white powder. The results are listed in Table 1.

Note:

In cases where more than one N—H group exists in the amide starting material, the amounts of PhI(OAc)₂ and Br₂ is multiplied by the number of N—H groups.

TABLE 1 Preparation of N-bromoamides N-Bromo- Yield, entry amide Method amide % 1 succinimide A NBS 92 2 succinimide B NBS up to 94 3 saccharin A NBSac 86 4 saccharin B NBSac 50 5 pthalimide A BPT 90 6 pthalimide B BPT 70 7 4-nitrophthalimide A BNPT 88 8 4-nitrophthalimide B BNPT 90 9 DMH B DBDMH 97 10 DPH A DBDPH 80 11 3,5,5-TMH A 1-BTMH 86 12 DMO A BDMO 84 13 DMO B BDMO up to 76

Entries 1-2: N-Bromosuccinimide, NBS ¹H NMR: δ 2.96 (s, 4H) ppm; ¹³C NMR: δ 173.2, 28.8 ppm.

Entries 3-4: N-Bromosaccharin, NBSac ¹H NMR (CD₃CN): δ 8.10-8.00 (m, 2H), 7.99-7.87 (m, 2H) ppm; ¹³C NMR (CD₃CN): δ 159.6, 139.3, 136.5, 135.9, 128.2, 126.4, 122.5 ppm.

Entries 5-6: N-Bromophthalimide, BPT ¹H NMR (CD₃CN): δ 7.84-7.76 (m, 4H) ppm; ¹³C NMR (CD₃CN): δ 166.7, 135.3, 133.4, 124.2 ppm.

Entries 7-8: N-Bromo-4-nitrophthalimide, BNPT ¹H NMR (CD₃CN): δ 8.58 (d, J=8.5 Hz, 1H), 8.55 (s, 1H) 8.04 (d, J=8.5 Hz, 1H) ppm; ¹³C NMR (CD₃CN): δ 165.2, 164.9, 152.6, 137.6, 134.3, 130.5, 125.6, 119.3 ppm.

Entry 9: 1,3-Dibromo-5,5-dimethylhydantoin in benzene, DBDMH ¹H NMR: δ 1.46 (s, 6H) ppm; ¹³C NMR: δ 172.2, 151.5, 68.9, 23.9 ppm.

Entry 10: 1,3-Dibromo-5,5-diphenylhydantoin, DBDPH ¹H NMR (CD₃CN): δ 7.51-7.43 (m, 6H), 7.32-7.28 (m, 4H) ppm; ¹³C NMR (CD₃CN): δ 171.4, 153.3, 137.0, 130.5, 129.7, 129.6, 129.3, 129.2, 80.1 ppm.

Entry 11: 1-Bromo-3,5,5-trimethylhydantoin, 1-BTMH ¹H NMR: δ 3.06 (s, 3H), 1.38 (s, 6H) ppm; ¹³C NMR: δ 174.7, 155.1, 66.1, 26.0, 23.3 ppm.

Entries 12-13: 3-Bromo-4,4-dimethyl-2-oxazolidinone, BDMO ¹H NMR: δ 4.19 (s, 2H), 1.29 (s, 6H) ppm; ¹³C NMR: δ 157.3, 74.8, 62.9, 24.1 ppm

Example 2 Comparative Examples

A. Attempts to Bromodecarboxylate Arenecarboxylic Acids with N-Bromosuccinimide (NBS) Under Heterolytic Reaction Conditions Disclosed in IN803DEL1999

The reactions were conducted under fluorescent room lighting (FL).

Example 2A-1

An attempt to bromodecarboxylate benzoic acid using tetrabutylammonium trifluororacetate as catalyst

A mixture of benzoic acid (0.44 g, 3.60 mmol), N-bromosuccinimide NBS (0.60 g, 3.37 mmol), tetrabutylammonium trifluororacetate [NBu₄]OAc_(F) (0.24 g, 0.67 mmol) and 1,2-dichloroethane DCE (6 mL) was stirred at rt for 24 h. The reaction mixture was washed with 1 M aq Na₂SO₃, dried over Na₂SO₄, and filtered through short neutral alumina pad.

The obtained filtrate did not contain bromobenzene (GC data, 1-chlro-2-fluorobenzene was used as internal standard).

Example 2A-2

An attempt to bromodecarboxylate p-toluic acid using tetrabutylammonium trifluororacetate as catalyst

A mixture of p-toluic acid (0.48 g, 3.52 mmol), N-bromosuccinimide NBS (0.60 g, 3.37 mmol), tetrabutylammonium trifluororacetate [NBu₄]OAc_(F) (0.24 g, 0.67 mmol) and 1,2-dichloroethane DCE (6 mL) was stirred at rt for 20 h. The reaction mixture was washed with 1 M aq Na₂SO₃, dried over Na₂SO₄, and filtered through short neutral alumina pad.

The obtained filtrate did not contain p-bromotoluene (GC data, o-dichlorobenzene was used as internal standard).

Example 2A-3

An attempt to bromodecarboxylate p-anisic acid using tetrabutylammonium trifluororacetate as catalyst

A mixture of p-anisic acid (0.52 g, 3.42 mmol), N-bromosuccinimide NBS (0.60 g, 3.37 mmol), tetrabutylammonium trifluororacetate [NBu₄]OAc_(F) (0.24 g, 0.67 mmol) and 1,2-dichloroethane DCE (6 mL) was stirred at rt for 18 h. The reaction mixture was washed with 1 M aq Na₂SO₃, dried over Na₂SO₄, and filtered through short neutral alumina pad.

The obtained filtrate did not contain p-bromoanisol (GC data, 1,2,4-trichlorobenzene was used as internal standard).

B. Attempts to Bromodecarboxylate Arenecarboxylic Acids with N-Bromosuccinimide (NBS) Under Heterolytic Reaction Conditions Disclosed in J. Dispersion Sci. Technol. 2007, v. 28, 613

Example 2B-1

An attempt to bromodecarboxylate 2-bromobenzoic acid using cetyltrimethylammonium bromide as catalyst

A mixture of 2-bromobenzoic acid (0.20 g, 1.0 mmol), N-bromosuccinimide NBS (0.27 g, 1.5 mmol), cetyltrimethylammonium bromide CTAB (1.82 g, 5.0 mmol) and 1,2-dichloroethane DCE (10 mL) was stirred under reflux conditions in dark for 3 h. After it was cooled, the reaction mixture was washed with 1 M aq Na₂SO₃, dried over Na₂SO₄, filtered through short neutral alumina pad and concentrated in vacuo to give 0.21 g (79%) of 2-chloroethyl 2-bromobenzoate 2-BrC₆H₄CO₂(CH₂)₂Cl.

¹H NMR: δ 7.85 (d, J=7 Hz, 1H), 7.64 (d, J=7 Hz, 1H), 7.38-7.28 (m, 2H) 4.56 (t, J=6 Hz, 2H), 3.80 (t, J=6 Hz, 2H) ppm.

Example 2B-2

An attempt to bromodecarboxylate 2-bromobenzoic acid using sodium dodecyl sulfate as catalyst

A mixture of 2-bromobenzoic acid (0.20 g, 1.0 mmol), N-bromosuccinimide NBS (0.27 g, 1.5 mmol), sodium dodecyl sulfate SDS (1.44 g, 5.0 mmol) and 1,2-dichloroethane DCE (10 mL) was stirred in dark for 3 h under reflux conditions. After it was cooled, the reaction mixture was washed with 1 M aq Na₂SO₃, dried over Na₂SO₄, filtered through short neutral alumina pad and concentrated in vacuo.

The residue (15 mg) did not contain 1,2-dibromobenzene by ¹H NMR.

Example 3 N-Bromoamides as Reagents for Radical Bromodecarboxylation N-Bromoamides Induced Bromodecarboxylation of 2-Bromobenzoic Acid

A mixture of 2-bromobenzoic acid (1 mmol), N-bromoamide, additive (optionally) and solvent (10 mL) was stirred under fluorescent room light illumination (FL). The reaction mixture was concentrated in vacuo. A solution of the residue in CDCl₃ was filtered directly to NMR tube. Conversion of the reaction was determined by ¹H NMR. The results are presented in Table 2.

TABLE 2 N-Bromoamides as reagents for radical bromodecarboxylation ^(a) entry Reaction conditions conversion, % 1 DBI 1 mol/DCM, rt FL 24 h 100 2 DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 100 3 NBS 1 mol/DCM, rt FL 24 h 0 4 NBS 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 0 5 DBDMH 1 mol/DCM, rt FL 24 h 0 6 DBDMH 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 6 7 BTMH 1 mol/DCM, rt FL 24 h 0 8 BTMH 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 0 9 BDMO 1 mol/DCM, rt FL 24 h 0 10 BDMO 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 1 11 BPT 1 mol/DCM, rt FL 24 h 0 12 BPT 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 7 13 BNPT 1 mol/DCM, rt FL 24 h 0 14 BNPT 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 0 15 NBSac 1 mol/DCM, rt FL 24 h 4 16 NBSac 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 17 ^(a) All quantities in mole/mole of 2-bromobenzoic acid.

Bromodecarboxylation of 2-bromobenzoic Acid with 1,3-dibromo-5,5-dimethylhydantoin

A mixture of 2-bromobenzoic acid (0.20 g, 1 mmol), 1,3-dibromo-5,5-dimethylhydantoin DBDMH (0.29 g, 1 mmol) and 1,2-dichloroethane DCE (5 mL) was irradiated with 250 W tungsten lamp under reflux conditions for 15 h. The cooled reaction mixture was washed with 1 M aq Na₂SO₃, dried over Na₂SO₄, filtered through short neutral alumina pad and concentrated in vacuo. The residue was purified by chromatography on silica gel (eluent: hexane) to give 50 mg (20%) of 1,2-dibromobenzene.

¹H NMR: δ 7.65-7.59 (m, 2H), 7.19-7.14 (m, 2H) ppm.

Bromodecarboxylation of 2-bromobenzoic Acid with N-bromosuccinimide

A mixture of 2-bromobenzoic acid (0.20 g, 1 mmol), N-bromosuccinimide NBS (0.36 g, 2 mmol) and 1,2-dichloroethane DCE (5 mL) was irradiated with 250 W tungsten lamp under reflux conditions for 15 h. The cooled reaction mixture was washed with 1 M aq Na₂SO₃, dried over Na₂SO₄, filtered through short neutral alumina pad and concentrated in vacuo. The residue was purified by chromatography on silica gel (eluent: hexane) to give 10 mg (4%) of 1,2-dibromobenzene.

Example 4 Bromodecarboxylation of 2-Bromobenzoic Acid Induced by Bromoisocyanurate Optimization of the Reaction Conditions

A round bottom flask equipped with Dimroth condenser (chilled to 10° C.) was charged with 2-bromobenzoic acid (1 mmol), bromoisocyanurate, additive (optionally) and solvent (10 mL). The mixture was stirred at rt or heated in an oil bath. The reaction was provided in the dark (NL) or under florescent room light irradiation (FL). The cold reaction mixture was concentrated in vacuo. The residue was dissolved in CDCl₃ and filtered directly to NMR tube. Conversion was determined by ¹H NMR. The results are presented in Table 3.

TABLE 3 Bromodecarboxylation of 2-bromobenzoic acid ^(a) entry Reaction conditions conversion, % 1 Br₂ 2 mol/DCM, rt FL 24 h 0 2 DBI 0.5 mol/DCM, 60° FL 24 h 30 3 DBI 0.75 mol/DCM, 60° FL 24 h 56 4 DBI 1 mol/DCM, rt FL 24 h 100 5 DBI 1 mol/Br₂ 0.5 mol/DCM, rt FL 24 h 100 6 DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 100 7 DBI 1 mol/Br₂ 2 mol/DCM, rt FL 24 h 100 8 DBI 1 mol/Br₂ 4 mol/DCM, rt FL 24 h 100 9 DBI 1 mol/BrCCl₃, rt FL 24 h 0 10 DBI 1 mol/BrCCl₃, 120° FL 1 h 11 11 DBI 1 mol/Br₂ 2 mol/BrCCl₃, rt FL 24 h 0 12 DBI 1 mol/Br₂ 2 mol/BrCCl₃, 120° FL 1 h 100 13 DBI 1 mol/Br₂ 2 mol/BrCCl₃, 120° NL, 1 h 39 14 DBI 1 mol/Br₂ 2 mol/BrCCl₃, 120° NL 3 h 100 15 DBI 1 mol/CCl₄, 100° FL 1 h 0 16 DBI 1 mol/Br₂ 2 mol/CCl₄, 100° FL 6 h 100 17 DBI 1 mol/CHCl₃, rt FL 24 h 0 18 DBI 1 mol/DCE, rt FL 24 h 6 19 DBI 1 mol/PhH, rt FL 24 h 0 20 DBI 1 mol/PhCl, rt FL 24 h 0 21 DBI 1 mol/PhCF₃, rt F, 24 h 0 22 DBI 1 mol/C₆H₁₂, rt FL 24 h 0 23 DBI 1 mol/EtOAc, rt FL 24 h 0 24 DBI 1 mol/MeCN, rt FL 24 h 33 25 DBI 1 mol/MeNO₂, rt FL 24 h 0 ^(a) All quantities in mole/mole of 2-bromobenzoic acid. Oil bath temperatures in degrees Celsius.

Example 5 Bromodecarboxylation of Arenecarboxylic Acids Optimizing of the Reactions

Mixture of arenecarboxylic acid (1 mmol), bromoisocyanurate, additive (optionally) and solvent (10 mL) was stirred under fluorescent room light irradiation (FL). An aliquot of the reaction mixture was concentrated in vacuo. The residue was dissolved in CDCl₃ and filtered directly to NMR tube. Conversion was determined by ¹H NMR. The results are presented in Table 4.

TABLE 4 Bromodecarboxylation of arenecarboxylic acids ArCO₂H ^(a) entry ArCO₂H Reaction conditions ^(a) conversion, % 1 2-NO₂C₆H₄CO₂H DBI 1 mol/DCM, rt FL 24 h 65 2 2-NO₂C₆H₄CO₂H DBI 1 mol/Br₂ 1 mol/DCM, 100 rt FL 24 h 3 2-NO₂C₆H₄CO₂H DBI 1 mol/Br₂ 2 mol/DCM, 100 rt FL 24 h 4 2-NO₂C₆H₄CO₂H DBI 1 mol/Br₂ 3 mol/DCM, 100 rt FL 24 h 5 2-NO₂C₆H₄CO₂H DBI 1 mol/Br₂ 4 mol/DCM, 100 rt FL 24 h 6 3-NO₂C₆H₄CO₂H DBI 1 mol/DCM, rt FL 24 h 18 7 3-NO₂C₆H₄CO₂H DBI 1 mol/Br₂ 1 mol/DCM, 100 rt FL 24 h 8 3-NO₂C₆H₄CO₂H DBI 1 mol/Br₂ 2 mol/DCM, 100 rt FL 24 h 9 3-NO₂C₆H₄CO₂H DBI 1 mol/Br₂ 3 mol/DCM, 100 rt FL 24 h 10 3-NO₂C₆H₄CO₂H DBI 1 mol/Br₂ 4 mol/DCM, 100 rt FL 24 h 11 4-NO₂C₆H₄CO₂H DBI 1 mol/DCM, rt FL 24 h 50 12 4-NO₂C₆H₄CO₂H DBI 1 mol/Br₂ 4 mol/DCM, 70 rt FL 24 h 13 4-NCC₆H₄CO₂H DBI 1 mol/DCM, rt FL 24 h 55 14 4-NCC₆H₄CO₂H DBI 1 mol/Br₂ 4 mol/DCM, 85 rt FL 24 h ^(a) All quantities in mole/mole of arenecarboxylic acid.

Example 6 Bromoisocyanurate Induced Radical Bromodecarboxylation of Arenecarboxylic Acids

A mixture of arenecarboxylic acid ArCO₂H (1 mmol), bromoisocyanurate, additive and solvent (10 mL) was stirred under fluorescent room light (FL) or warm-white 3 W LED (LL) irradiation (hv). The reaction mixture washed with 1 M aq Na₂SO₃, dried over Na₂SO₄, filtered through short neutral alumina pad and concentrated in vacuo to yield crude bromoarene ArBr. Optionally, the crude bromide was purified by chromatography on silica gel. The results are presented in Table 5.

TABLE 5 Bromodecarboxylation of arenecarboxylic acids ArCO₂H ^(a) yield, % entry ArCO₂H Reaction conditions ArBr  1 2-BrC₆H₄CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 97  2 3-BrC₆H₄CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 92  3 4-BrC₆H₄CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 82  4 2-ClC₆H₄CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 98  5 3-ClC₆H₄CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 89  6 4-ClC₆H₄CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 88  7 2,4-Cl₂C₆H₃CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 97  8 2-NO₂C₆H₄CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 99  9 3-NO₂C₆H₄CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 99 10 4-NO₂C₆H₄CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 60 11 3-CNC₆H₄CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 66 12 4-CNC₆H₄CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 95 13 2-Br-5-FC₆H₃CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 96 14 5-Br-2-FC₆H₃CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 36 15 5-Br-2-FC₆H₃CO₂H DBI 1 mol/Br₂ 2 mol/DCM, 60° FL 24 h 89 16 4-Cl-2-FC₆H₃CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 60 17 4-NO₂-2-CF₃C₆H₃CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 20 18 4-NO₂-2-CF₃C₆H₃CO₂H DBI 1 mol/Br₂ 2 mol/DCM, 60° FL 24 h 92 19 4-NO₂-3-CF₃C₆H₃CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 45 20 2-MeO₂CC₆H₄CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 98 21 3-MeO₂CC₆H₄CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 98 22 4-MeO₂CC₆H₄CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 97 23 3-NO₂-4-MeO₂CC₆H₃CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 75 24 2-PhtNC₆H₄CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 99 25 trimellitic anhydride DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 70 26

DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 71 27 3,5-Br₂C₆H₃CO₂H DBI 1 mol/Br₂ 1 mol/DCM, rt FL 24 h 51 (GC) 28 3,4-F₂C₆H₃CO₂H DBI 1 mol/Br₂ 2 mol/CBrCl₃, 120° LL 24 h 77 (GC) 29 2,4,5-F₃C₆H₂CO₂H DBI 1 mol/Br₂ 2 mol/CBrCl₃, 120° LL 24 h 95 (GC) 30 3,4,5-F₃C₆H₂CO₂H DBI 1 mol/Br₂ 2 mol/CBrCl₃, 120° LL 24 h 86 (GC) 31 C₆F₅CO₂H DBI 1 mol/Br₂ 1 mol/CBrCl₃, 120° LL 24 h 70 (GC) ^(a) All quantities in mole/mole of arenecarboxylic acid. Oil bath temperatures in degrees Celsius.

Entry 1: 1,2-Dibromobenzene ¹H NMR: δ 7.62 (dd, J=6, 4 Hz, 2H), 7.16 (dd, J=6, 4 Hz, 2H) ppm; ¹³C NMR: δ 133.9, 128.6, 124.9 ppm.

Entry 2: 1,3-Dibromobenzene ¹H NMR: δ 7.67 (t, J=2 Hz, 1H), 7.43 (dd, J=8, 2 Hz, 2H), 7.1 (t, J=8 Hz, 1H) ppm; ¹³C NMR: δ 134.3, 131.2, 130.3, 123.1 ppm.

Entry 3: 1,4-Dibromobenzene ¹H NMR: δ 7.35 (s, 4H) ppm; ¹³C NMR: δ 133.2, 121.1 ppm.

Entry 4: 1-Bromo-2-chlorobenzene ¹H NMR: δ 7.61 (dd, J=8, 1.4 Hz, 1H), 7.45 (dd, J=8, 1.4 Hz, 1H), 7.24 (td, J=8, 1.4 Hz, 1H), 7.11 (td, J=8, 1.4 Hz, 1H) ppm; ¹³C NMR: δ 134.6, 133.9, 130.5, 128.5, 127.9, 122.6 ppm.

Entry 5: 1-Bromo-3-chlorobenzene ¹H NMR: δ 7.52 (t, J=2 Hz, 1H), 7.39 (d, J=8 Hz, 1H), 7.28 (d, J=8 Hz, 1H), 7.16 (t, J=8 Hz, 1H) ppm; ¹³C NMR: δ 135.3, 131.6, 130.9, 129.9, 127.4, 122.9 ppm.

Entry 6: 1-Bromo-4-chlorobenzene ¹H NMR: δ 7.42 (dt, J=9, 3 Hz, 2H), 7.10-7.22 (m, 2H) ppm; ¹³C NMR: δ 133.3, 132.9, 130.3, 120.4 ppm.

Entry 7: 1-Bromo-2,4-dichlorobenzene ¹H NMR: δ 7.52 (d, J=9 Hz, 1H), 7.45 (d, J=2 Hz, 1H), 7.10 (dd, J=9, 2 Hz, 1H) ppm; ¹³C NMR: δ 135.5, 134.4, 133.9, 130.3, 128.3, 120.8 ppm.

Entry 8: 1-Bromo-2-nitrobenzene ¹H NMR: δ 7.84 (dd, J=8, 2 Hz, 1H), 7.74 (dd, J=8, 2 Hz, 1H), 7.49-7.40 (m, 2H) ppm; ¹³C NMR: δ 150.1, 135.2, 133.3, 128.3, 125.7, 114.6 ppm.

Entry 9: 1-Bromo-3-nitrobenzene ¹H NMR: δ 8.38 (t, J=1 Hz, 1H), 8.17 (dd, J=8, 1 Hz, 1H), 7.83 (dd, J=8, 1 Hz, 1H), 7.44 (t, J=8 Hz, 1H) ppm; ¹³C NMR: δ 148.9, 137.7, 130.7, 126.9, 123.0, 122.2 ppm.

Entry 10: 1-Bromo-4-nitrobenzene ¹H NMR: δ 8.08 (d, J=9 Hz, 2H), 7.67 (d, J=9 Hz, 2H) ppm; ¹³C NMR: δ 147.1, 132.7, 130.1, 125.1 ppm.

Entry 11: 3-Bromobenzonitrile ¹H NMR: δ 7.79 (s, 1H), 7.74 (d, J=8 Hz, 1H), 7.60 (d, J=8 Hz, 1H), 7.36 (t, J=8 Hz, 1H) ppm; ¹³C NMR: δ 136.2, 134.9, 130.8, 130.7, 123.0, 117.4, 114.3 ppm.

Entry 12: 4-Bromobenzonitrile ¹H NMR: δ 7.63 (d, J=9 Hz, 2H), 7.52 (d, J=9 Hz, 2H) ppm; ¹³C NMR: δ 133.5, 132.7, 128.1, 118.1, 111.4 ppm.

Entry 13: 1,2-Dibromo-4-fluorobenzene ¹H NMR: δ 7.57 (dd, J=9, 6 Hz, 1H), 7.37 (dd, J=8, 3 Hz, 1H), 6.29 (td, J=6, 39 Hz, 1H) ppm; ¹³C NMR: δ 161.5 (d, J_(CF)=251 Hz), 134.4 (d, J_(CF)=9 Hz), 125.3 (d, J_(CF)=10 Hz), 121.3, 121.1, 119.7 (d, J_(CF)=4 Hz) ppm.

Entries 14-15: 2,4-Dibromo-1-fluorobenzene ¹H NMR: δ 7.69 (dd, J=6, 2 Hz, 1H), 7.39 (ddd, J=9, 4, 2 Hz, 1H), 7.01 (t, J=9 Hz, 1H) ppm; ¹³C NMR: δ 158.5 (d, J_(CF)=248 Hz), 136.0, 132.1 (d, J_(CF)=7 Hz), 117.9 (d, J_(CF)=24 Hz), 117.1 (d, J_(CF)=4 Hz), 110.3 (d, J_(CF)=22 Hz), ppm.

Entry 16: 1-Bromo-4-chloro-2-fluorobenzene ¹H NMR: δ 7.47 (t, J=8 Hz, 1H), 7.15 (dd, J=8, 2 Hz, 1H), 7.04 (d, J=8 Hz, 1H) ppm; ¹³C NMR: δ 159.1 (d, J_(CF)=250 Hz), 134.1, 125.8 (d, J_(CF)=4 Hz), 117.5 (d, J_(CF)=25 Hz), 107.4 (d, J_(CF)=21 Hz) ppm.

Entry 17-18: 1-Bromo-4-nitro-2-(trifluoromethyl)benzene ¹H NMR: δ 8.50 (d, J=2 Hz, 1H), 8.26 (dd, J=9, 2 Hz, 1H), 7.96 (d, J=9 Hz, 1H) ppm; ¹³C NMR: δ 146.9, 136.5, 131.8 (d, J_(CF)=33 Hz), 127.7, 127.5, 123.2 (q, J_(CF)=6 Hz), 122.0 (q, J_(CF)=274 Hz) ppm; ¹⁹F NMR: δ −66.4 ppm.

Entry 19: 4-Bromo-1-nitro-2-(trifluoromethyl)benzene ¹H NMR: δ 7.97 (d, J=2 Hz, 1H), 7.87 (dd, J=9, 2 Hz, 1H), 7.80 (d, J=9 Hz, 1H) ppm; ¹³C NMR: δ 147.0, 136.3, 131.4 (q, J_(CF)=11, 5 Hz), 127.4, 126.7, 125.5 (d, J_(CF)=35 Hz), 121.2 (q, J_(CF)=274 Hz) ppm; ¹⁹F NMR: δ −63.3 ppm.

Entry 20: Methyl 2-bromobenzoate ¹H NMR: δ 7.74 (d, J=8 Hz, 1H), 7.60 (d, J=8 Hz, 1H), 7.34-7.24 (m, 2H), 3.88 (s, 3H) ppm; ¹³C NMR: δ 166.5, 134.3, 132.5, 132.1, 131.2, 127.1, 121.6, 52.4 ppm.

Entry 21: Methyl 3-bromobenzoate ¹H NMR: δ 8.16 (s, 1H), 7.95 (d, J=8 Hz, 1H), 7.66 (d, J=8 Hz, 1H), 7.30 (t, J=8 Hz, 3H), 3.91 (s, 3H) ppm; ¹³C NMR: δ 165.8, 135.9, 132.7, 132.1, 130.0, 128.2, 122.5, 55.5 ppm

Entry 22: Methyl 4-bromobenzoate ¹H NMR: δ 7.89 (d, J=8 Hz, 2H), 7.57 (d, J=8 Hz, 2H), 3.91 (s, 3H) ppm; ¹³C NMR: δ 166.5, 131.8, 131.2, 129.1, 128.1, 52.4 ppm.

Entry 23: Methyl 4-bromo-2-nitrobenzoate ¹H NMR: δ 8.00 (d, J=2 Hz, 1H), 7.79 (dd, J=8, 2 Hz, 1H), 7.64 (d, J=2 Hz, 1H), 3.90 (s, 3H) ppm; ¹³C NMR: δ 164.9, 149.0, 135.9, 131.4, 127.1, 125.9, 125.8, 53.5 ppm.

Entry 24: 1-Bromo-2-phthalimidobenzene ¹H NMR: δ 8.00-7.95 (m, 2H), 7.84-7.78 (m, 2H), 7.74 (dd, J=8, 1 Hz, 1H), 7.47 (dt, J=8, 1 Hz, 1H), 7.40-7.32 (m, 2H) ppm; ¹³C NMR: δ 166.7, 134.6, 133.7, 132.0, 131.5, 131.0, 130.9, 128.5, 124.1, 123.4 ppm;

Entry 25: 4-Bromophthalic anhydride ¹H NMR: δ 8.16 (d, J=1 Hz, 1H), 8.04 (dd, J=8, 1 Hz, 1H), 7.88 (d, J=8 Hz, 1H) ppm; ¹³C NMR: δ 161.9, 161.5, 139.4, 133.0, 131.6, 129.9, 129.0, 127.0 ppm.

Entry 26: N-(tert-Butyl)-4-bromophthalimide ¹H NMR: δ 7.88 (d, J=1 Hz, 1H), 7.80 (dd, J=8, 1 Hz, 1H), 7.62 (d, J=8 Hz, 1H), 1.68 (s, 3H) ppm; ¹³C NMR: δ 168.9, 168.3, 136.8, 133.9, 130.8, 128.6, 126.1, 124.2, 58.3, 29.1 ppm.

Example 7 Bromodecarboxylation of Arenedicarboxylic Acids Induced by Bromoisocyanurate

Round bottom flask equipped with Dimroth condenser (chilled to 10° C.) was charged with arenedicarboxylic acid RC₆H₃(CO₂H)₂ (1 mmol), bromoisocyanurate, additive and solvent (10 mL). The mixture was magnetically stirred and heated in an oil bath at 120° C. under florescent room light irradiation (FL) for 60 h. The cooled reaction mixture was filtered through short silica gel pad, washed with 1 M aq Na₂SO₃, dried over Na₂SO₄, filtered and concentrated in vacuo to give crude dibromoarene RC₆H₃Br₂. Optionally, the crude dibromide was purified by chromatography on silica gel. The results are presented in Table 6.

TABLE 6 Bromodecarboxylation of arenedicarboxylic acids RC₆H₃(CO₂H)₂ ^(a) Yield, % entry RC₆H₃(CO₂H)₂ Reaction conditions RC₆H₃Br₂ 1 4-NO₂-1,2-C₆H₃(CO₂H)₂ DBI 2 mol/Br₂ 2 mol/ 32 BrCCl₃, 120° FL 2 h 2 1,3-C₆H₄(CO₂H)₂ DBI 2 mol/Br₂ 2 mol/ 6 BrCCl₃, 120° FL 2 h 3 1,3-C₆H₄(CO₂H)₂ DBI 2 mol/Br₂ 2 mol/ 12 BrCCl₃, 120° FL 24 h 4 1,3-C₆H₄(CO₂H)₂ DBI 2 mol/Br₂ 2 mol/ 17 BrCCl₃, 120° FL 60 h 5 5-NO₂-1,3-C₆H₃(CO₂H)₂ DBI 2 mol/Br₂ 2 mol/ 17 BrCCl₃, 120° FL 2 h 6 5-NO₂-1,3-C₆H₃(CO₂H)₂ DBI 2 mol/Br₂ 2 mol/ 20 BrCCl₃, 120° FL 24 h 7 5-NO₂-1,3-C₆H₃(CO₂H)₂ DBI 2 mol/Br₂ 2 mol/ 25 BrCCl₃, 120° FL 60 h 8 1,4-C₆H₄(CO₂H)₂ DBI 2 mol/Br₂ 2 mol/ 12 BrCCl₃, 120° FL 2 h ^(a) All quantities in mole/mole of arenedicarboxylic acid. Oil bath temperatures in degrees Celsius.

Example 8 Bromoisocyanurate Induced Radical Bromodecarboxylation of Alkanoic Acids

Bromodecarboxylation of Lauric Acid: Optimization of the Reaction Conditions

A mixture of lauric acid (0.5 mmol), bromoisocyanurate, additive (optionally), and DCM (4 mL) was stirred under fluorescent room light (FL) or warm-white 3 W LED lamp irradiation (LL), or in the dark (NL). An aliquot of the reaction mixture washed with 1 M aq Na₂SO₃, dried over Na₂SO₄, and filtered through short neutral silica gel pad. The yield of 1-bromoundecane was determined by gas chromatography (GC) using 1,2,4,5-tetrachlorobenzene as internal standard. The results are presented in Table 7.

TABLE 7 Bromodecarboxylation of lauric acid ^(a) yield, entry Reaction conditions % ^(b)  1 DBI 1 mol/DCM, rt FL 1 h  0  2 DBI 1 mol/DCM, rt FL 4 h  0  3 DBI 1 mol/DCM, rt FL 21 h  58  4 DBI 1 mol/Br₂ 0.1 mol/DCM, rt FL 1 h  8  5 DBI 1 mol/Br₂ 0.1 mol/DCM, rt FL 2 h  17  6 DBI 1 mol/Br₂ 0.1 mol/DCM, rt FL 3 h  24  7 DBI 1 mol/Br₂ 0.1 mol/DCM, rt FL 4 h  31  8 DBI 1 mol/Br₂ 0.2 mol/DCM, rt FL 1 h  20  9 DBI 1 mol/Br₂ 0.2 mol/DCM, rt FL 2 h  39  10 DBI 1 mol/Br₂ 0.2 mol/DCM, rt FL 3 h  62  11 DBI 1 mol/Br₂ 0.2 mol/DCM, rt FL 4 h  79  12 DBI 1 mol/Br₂ 0.2 mol/DCM, rt FL 5 h  79  13 DBI 1 mol/Br₂ 0.3 mol/DCM, rt FL 1 h  25  14 DBI 1 mol/Br₂ 0.3 mol/DCM, rt FL 2 h  51  15 DBI 1 mol/Br₂ 0.3 mol/DCM, rt FL 3 h  72  16 DBI 1 mol/Br₂ 0.3 mol/DCM, rt FL 4 h  83  17 DBI 1 mol/Br₂ 0.3 mol/DCM, rt FL 5 h  80  18 DBI 1 mol/Br₂ 0.4 mol/DCM, rt FL 1 h  23  19 DBI 1 mol/Br₂ 0.4 mol/DCM, rt FL 2 h  50  20 DBI 1 mol/Br₂ 04 mol/DCM, rt FL 3 h  70  21 DBI 1 mol/Br₂ 0.4 mol/DCM, rt FL 4 h  80  22 DBI 1 mol/Br₂ 0.5 mol/DCM, rt FL 1 h  36  23 DBI 1 mol/Br₂ 0.5 mol/DCM, rt FL 2 h  70  24 DBI 1 mol/Br₂ 0.5 mol/DCM, rt FL 3 h  82  25 DBI 1 mol/Br₂ 0.5 mol/DCM, rt FL 4 h  71  26 DBI 1 mol/Br₂ 1 mol/DCM, rt FL 1 h  43  27 DBI 1 mol/Br₂ 1 mol/DCM, rt FL 2 h  73  28 DBI 1 mol/Br₂ 1 mol/DCM, rt FL 3 h  70  29 DBI 1 mol/Br₂ 1 mol/DCM, rt FL 4 h  60  30 DBI 1 mol/Br₂ 2 mol/DCM, rt FL 1 h  55  31 DBI 1 mol/Br₂ 2 mol/DCM, rt FL 2 h  78  32 DBI 1 mol/Br₂ 2 mol/DCM, rt FL 3 h  70  33 DBI 1 mol/Br₂ 0.3 mol/DCM, rt NL 2 h  1  34 DBI 1 mol/Br₂ 0.3 mol/DCM, rt NL 4 h  2  35 DBI 1 mol/Br₂ 0.3 mol/DCM, rt NL 8 h  3  36 DBI 1 mol/Br₂ 0.3 mol/DCM, rt NL 24 h  4  37 DBI 1 mol/Br₂ 0.3 mol/DCM, 3° FL 2 h  8  38 DBI 1 mol/Br₂ 0.3 mol/DCM, 3° FL 4 h  19  39 DBI 1 mol/Br₂ 0.3 mol/DCM, 3° FL 8 h  41  40 DBI 1 mol/Br₂ 0.3 mol/DCM, 3° FL 24 h  79  41 DBI 1 mol/I₂ 0.3 mol/DCM, rt FL 1 h  0  42 DBI 1 mol/I₂ 0.3 mol/DCM, rt FL 2 h  9  43 DBI 1 mol/I₂ 0.3 mol/DCM, rt FL 5.5 h  31  44 DBI 1 mol/I₂ 0.3 mol/DCM, rt FL 19 h  35  45 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 1 h  25  46 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 2 h  62  47 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 3 h  84  48 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 4 h  98  49 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 5 h  96  50 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 20 h  71  51 DBI 1 mol/[NBu₄]Br₃ 0.1 mol/DCM, rt FL 4 h  78  52 DBI 1 mol/[NBu₄]Br₃ 0.1 mol/DCM, rt FL 5 h  92  53 DBI 1 mol/[NBu₄]Br₃ 0.1 mol/DCM, rt FL 6 h  95  54 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/TEMPO 0.1 mol/DCM, rt FL 1 h  0  55 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/TEMPO 0.1 mol/DCM, rt FL 2 h  0  56 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/TEMPO 0.1 mol/DCM, rt FL 4 h  1  57 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt LL 1 h  82  58 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt LL 2 h  66  59 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, 0° LL 1 h  67  60 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, 0° LL 2 h  93  61 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, 0° LL 3 h 100  62 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, 0° LL 4 h  95  63 DBI 0.5 mol/[NBu₄]Br₃ 0.3 mol/DCM, 0° LL 1 h  40  64 DBI 0.5 mol/[NBu₄]Br₃ 0.3 mol/DCM, 0° LL 2 h  70  65 DBI 0.5 mol/[NBu₄]Br₃ 0.3 mol/DCM, 0° LL 3 h  78  66 DBI 0.5 mol/[NBu₄]Br₃ 0.3 mol/DCM, 0° LL 4 h  79  67 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, −20° LL 1 h  5  68 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, −20° LL 2 h  11  69 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, −20° LL 3 h  15  70 DBI 1 mol/[NEt₄]Br₃ 0.3 mol/Br₂ 0.3 mol/DCM, rt FL 1 h  11  71 DBI 1 mol/[NEt₄]Br₃ 0.3 mol/Br₂ 0.3 mol/DCM, rt FL 2 h  25  72 DBI 1 mol/[NEt₄]Br₃ 0.3 mol/Br₂ 0.3 mol/DCM, rt FL 4 h  54  73 DBI 1 mol/[NEt₄]Br₃ 0.3 mol/Br₂ 0.3 mol/DCM, rt FL 6 h  83  74 DBI 1 mol/[NEt₄]Br₃ 0.3 mol/DCM, rt FL 1 h  18  75 DBI 1 mol/[NEt₄]Br₃ 0.3 mol/DCM, rt FL 4 h  68  76 DBI 1 mol/[NEt₄]Br₃ 0.3 mol/DCM, rt FL 6 h  94  77 DBI 1 mol/[N(C₆H₁₃)₄]Br 0.3 mol/Br₂ 0.3 mol/DCM, rt FL 1 h  16  78 DBI 1 mol/[N(C₆H₁₃)₄]Br 0.3 mol/Br₂ 0.3 mol/DCM, rt FL 4 h  67  79 DBI 1 mol/[N(C₆H₁₃)₄]Br 0.3 mol/Br₂ 0.3 mol/DCM, rt FL 6 h  85  80 DBI 1 mol/[BuNEt₃]Br 0.3 mol/Br₂ 0.3 mol/DCM, 0° LL 1 h  41  81 DBI 1 mol/[BuNEt₃]Br 0.3 mol/Br₂ 0.3 mol/DCM, 0° LL 2 h  77  82 DBI 1 mol/[BuNEt₃]Br 0.3 mol/Br₂ 0.3 mol/DCM, 0° LL 3 h  95  83 DBI 1 mol/[BuNEt₃]Br 0.3 mol/Br₂ 0.3 mol/DCM, 0° LL 4 h 100  84 DBI 1 mol/[MeN(C₈H₁₇)₃]Br 0.3 mol/Br₂ 0.3 mol/DCM, rt FL 1 h  9  85 DBI 1 mol/[MeN(C₈H₁₇)₃]Br 0.3 mol/Br₂ 0.3 mol/DCM, rt FL 2 h  22  86 DBI 1 mol/[MeN(C₈H₁₇)₃]Br 0.3 mol/Br₂ 0.3 mol/DCM, rt FL 4 h  48  87 DBI 1 mol/[MeN(C₈H₁₇)₃]Br 0.3 mol/Br₂ 0.3 mol/DCM, rt FL 6 h  72  88 DBI 1 mol/[PhNMe₃]Br₃ 0.3 mol/DCM, rt FL 4 h  79  89 DBI 1 mol/[PhCH₂NMe₃]Br₃ 0.3 mol/DCM, rt FL 1 h  8  90 DBI 1 mol/[PhCH₂NMe₃]Br₃ 0.3 mol/DCM, rt FL 4 h  83  91 DBI 1 mol/[PhCH₂NMe₃]Br₃ 0.3 mol/DCM, rt FL 6 h  89  92 DBI 1 mol/[C₅H₅NH]Br₃ 0.3 mol/DCM, rt FL 4 h  76  93 DBI 1 mol/[DBUH]Br₃ 0.3 mol/DCM, 0° LL 1 h  57  94 DBI 1 mol/[DBUH]Br₃ 0.3 mol/DCM, 0° LL 2 h  86  95 DBI 1 mol/[DBUH]Br₃ 0.3 mol/DCM, 0° LL 3 h  94  96 DBI 1 mol/[PBu₄]Br 0.3 mol/Br₂ 0.3 mol/DCM, rt FL 1 h  19  97 DBI 1 mol/[PBu₄]Br 0.3 mol/Br₂ 0.3 mol/DCM, rt FL 4 h  87  98 DBI 1 mol/[PBu₄]Br 0.3 mol/Br₂ 0.3 mol/DCM, rt FL 6 h  81  99

 36 100

 73 101

 95 102

100 103

 40 104

 95 ^(a) All quantities in mole/mole of lauric acid. Water/ice/salt bath temperatures in degrees Celsius. ^(b) 1-Bromoundecane analyzed by GC.

Example 9 Bromodecarboxylation of Cyclohexanecarboxylic Acid Optimization of the Reaction Conditions

A mixture of cyclohexanecarboxylic acid (0.5 mmol), bromoisocyanurate, additive (optionally) and solvent (4 mL) was stirred under fluorescent room light irradiation (FL). An aliquot of the reaction mixture washed with 1 M aq Na₂SO₃, dried over Na₂SO₄, and filtered through short neutral silica gel pad. The yield of bromocyclohexane was determined by gas chromatography (GC) using 1,2,4,5-tetrachlorobenzene as internal standard. The results are presented in Table 8.

TABLE 8 Bromodecarboxylation of cyclohexanecarboxylic acid ^(a) entry Reaction conditions yield % ^(b) 1 DBI 1 mol/Br₂ 0.2 mol/DCM, rt FL 1 h 10 2 DBI 1 mol/Br₂ 0.2 mol/DCM, rt FL 2 h 23 3 DBI 1 mol/Br₂ 0.2 mol/DCM, rt FL 3 h 35 4 DBI 1 mol/Br₂ 0.2 mol/DCM, rt FL 4 h 43 5 DBI 1 mol/Br₂ 0.3 mol/DCM, rt FL 1 h 23 6 DBI 1 mol/Br₂ 0.3 mol/DCM, rt FL 2 h 47 7 DBI 1 mol/Br₂ 0.3 mol/DCM, rt FL 3 h 70 8 DBI 1 mol/Br₂ 0.3 mol/DCM, rt FL 4 h 62 9 DBI 1 mol/Br₂ 0.4 mol/DCM, rt FL 1 h 23 10 DBI 1 mol/Br₂ 0.4 mol/DCM, rt FL 2 h 49 11 DBI 1 mol/Br₂ 0.4 mol/DCM, rt FL 3 h 55 12 DBI 1 mol/Br₂ 0.4 mol/DCM, rt FL 4 h 51 ^(a) All quantities in mole/mole of cyclohexanecarboxylic acid. ^(b) Bromocyclohexane analyzed by GC.

Example 10 Bromodecarboxylation of 2-methylcaproic Acid Optimization of the Reaction Conditions

A mixture of 2-methylcaproic acid (0.5 mmol), bromoisocyanurate, additive (optionally) and solvent (4 mL) was stirred under fluorescent room light irradiation (FL). An aliquot of the reaction mixture washed with 1 M aq Na₂SO₃, dried over Na₂SO₄, and filtered through short neutral silica gel pad. The yield of 2-bromohexane was determined by gas chromatography (GC) using 1,2,4,5-tetrachlorobenzene as internal standard. The results are presented in Table 9.

TABLE 9 Bromodecarboxylation of 2-methylcaproic acid ^(a) entry Reaction conditions yield % ^(b) 1 DBI 1 mol/[NBu₄]Br₃ 0.1 mol/DCM, rt FL 1 h 10 2 DBI 1 mol/[NBu₄]Br₃ 0.1 mol/DCM, rt FL 3 h 34 3 DBI 1 mol/[NBu₄]Br₃ 0.1 mol/DCM, rt FL 5 h 59 4 DBI 1 mol/[NBu₄]Br₃ 0.1 mol/DCM, rt FL 19 h 72 5 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 1 h 19 6 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 3 h 59 7 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 5 h 79 8 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 7 h 73 9 DBI 1 mol/[NBu₄]Br₃ 0.5 mol/DCM, rt FL 1 h 33 10 DBI 1 mol/[NBu₄]Br₃ 0.5 mol/DCM, rt FL 2 h 67 11 DBI 1 mol/[NBu₄]Br₃ 0.5 mol/DCM, rt FL 3 h 87 12 DBI 1 mol/[NBu₄]Br₃ 0.5 mol/DCM, rt FL 4 h 85 13 DBI 1 mol/[NBu₄]Br₃ 0.7 mol/DCM, rt FL 1 h 33 14 DBI 1 mol/[NBu₄]Br₃ 0.7 mol/DCM, rt FL 3 h 88 15 DBI 1 mol/[NBu₄]Br₃ 0.7 mol/DCM, rt FL 4 h 86 ^(a) All quantities in mole/mole of 2-methylcaproic acid. ^(b) 2-Bromohexane analyzed by GC.

Example 11 Bromodecarboxylation of 4-Chlorophenylacetic Acid Optimization of the Reaction Conditions

A mixture of 4-chlorophenylacetic acid ArCH₂CO₂H (Ar=4-ClC₆H₄) (1 mmol), bromoisocyanurate, additive (optionally) and solvent (6 mL) was stirred under fluorescent room light irradiation (FL). An aliquot of the reaction mixture was washed with 1 M aq Na₂SO₃, dried over Na₂SO₄, and filtered through short neutral silica gel pad. The yields of 4-chlorobenzyl bromide ArCH₂Br and 4-chlorobenzal bromide ArCHBr₂ were determined by gas chromatography (GC) using 1,2,4-trichlorobenzene as internal standard. The results are presented in Table 10.

TABLE 10 Bromodecarboxylation of 4-chlorophenylacetic acid ArCH₂CO₂H (Ar = 4-ClC₆H₄)^(a) GC yield, % ArCH₂Br/ entry Reaction conditions ArCHBr₂ 1 DBI 1 mol/Br₂ 0.3 mol/DCM, FL rt 0.5 h  8:5 2 DBI 1 mol/Br₂ 0.3 mol/DCM, FL rt 1 h  7:13 3 DBI 1 mol/Br₂ 0.3 mol/DCM, FL rt 2 h  4:23 4 DBI 1 mol/[NBu₄]Br 0.5 mol/DCM, FL rt 1 h 36:0 5 DBI 1 mol/[NBu₄]Br 0.5 mol/DCM, FL rt 2 h 66:0 6 DBI 1 mol/[NBu₄]Br 0.5 mol/DCM, FL rt 3 h 67:0 7 DBI 1 mol/[NBu₄]Br 0.5 mol/DCM, FL rt 22 h 53:0 8 DBI 1 mol/[NBu₄]Br 0.5 mol/Br₂ 0.5 mol/DCM, 82:0 FL rt 1 h 9 DBI 1 mol/[NBu₄]Br 0.5 mol/Br₂ 0.5 mol/DCM, 83:1 FL rt 2 h 10 DBI 1 mol/[NBu₄]Br₃ 0.5 mol/DCM, FL rt 1 h 92:0 11 DBI 1 mol/[NBu₄]Br₃ 0.5 mol/DCM, FL rt 2 h 92:1 12 DBI 1 mol/[NBu₄]Br₃ 0.5 mol/DCM, FL rt 3 days 68:8 13 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, FL rt 1 h 95:0 14 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, FL rt 2 h 94:2 15 DBI 1 mol/[NBu₄]Br₃ 0.2 mol/DCM, FL rt 1 h 79:0 16 DBI 1 mol/[NBu₄]Br₃ 0.2 mol/DCM, FL rt 2 h 93:2 17 DBI 1 mol/[NBu₄]Br₃ 0.1 mol/DCM, FL rt 1 h 59:0 18 DBI 1 mol/[NBu₄]Br₃ 0.1 mol/DCM, FL rt 2 h 91:1 19 DBI 1 mol/[NBu₄]Br₃ 0.1 mol/DCM, FL rt 3 h 87:3 20 DBI 1 mol/[NBu₄]Br₃ 0.05 mol/DCM, FL rt 2 h 78:1 21 DBI 1 mol/[NBu₄]Br₃ 0.05 mol/DCM, FL rt 3 h 84:2 21 DBI 1 mol/[NBu₄]Br₃ 0.05 mol/DCM, FL rt 4 h 81:4 ^(a)All quantities in mole/mole of 4-chlorophenylacetic acid.

Example 12 Bromodecarboxylation of Alkanoic Acids

A mixture of alkanoic acid RCO₂H (2 mmol), bromoisocyanurate, additive (optionally) and solvent (12 mL) was stirred under fluorescent room light irradiation (FL). The reaction mixture washed with 1 M aq Na₂SO₃, dried over Na₂SO₄, filtered through short silica gel pad and concentrated in vacuo to yield crude alkyl bromide RBr. Optionally, the crude bromide was purified by chromatography on silica gel. The results are presented in Table 11.

TABLE 11 Bromodecarboxylation of alkanoic acids RCO₂H ^(a) yield, % entry RCO₂H Reaction conditions RBr  1 H(CH₂)₁₁CO₂H DBI 1 mol/Br₂ 0.3 mol/DCM, 84 rt FL 4 h  2 H(CH₂)₁₁CO₂H DBI 1 mol/[NBu₄]Br₃ 0.1 mol/  95^(b) DCM, rt FL 5 h  3 c-C₆H₁₁(CH₂)₂CO₂H DBI 1 mol/[NBu₄]Br₃ 0.3 mol/ 89 DCM, rt FL 4 h  4 Br(CH₂)₁₀CO₂H DBI 1 mol/Br₂ 0.3 mol/DCM, 85 rt FL 4 h  5 MeO₂C(CH₂)₆CO₂H DBI 1 mol/Br₂ 0.3 mol/DCM, 83 rt FL 4 h  6 4-ClC₆H₄CO(CH₂)₂CO₂H DBI 1 mol/Br₂ 0.3 mol/DCM, 99 rt FL 4 h  7 PhCO(CH₂)₃CO₂H DBI 1 mol/[NBu₄]Br₃ 0.1 mol/ 69 DCM, rt FL 5 h  8 PhCO(CH₂)₄CO₂H DBI 1 mol/[NBu₄]Br₃ 0.3 mol/ 84 DCM, rt FL 4 h  9 PhCH₂CO₂H DBI 1 mol/[NBu₄]Br₃ 0.1 mol/ 90 DCM, rt FL 2 h 10 4-ClC₆H₄CH₂CO₂H DBI 1 mol/[NBu₄]Br₃ 0.1 mol/ 97 DCM, rt FL 2 h 11 4-PhC₆H₄CH₂CO₂H DBI 1 mol/[NBu₄]Br₃ 0.1 mol/ 82 DCM, rt FL 2 h 12 PhCHMeCO₂H DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ 87 DCM, rt FL 3 h 13 H(CH₂)₄CHMeCO₂H DBI 1 mol/[NBu₄]Br₃ 0.5 mol/  97^(b) DCM, rt FL 3 h 14 H(CH₂)₁₆CHMeCO₂H DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ 92 DCM, rt FL 4 h 15 Et₂C(CO₂Et)CO₂H DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ 85 DCM, rt FL 4 h 16 c-C₄H₉CO₂H DBI 1 mol/[NBu₄]Br₃ 0.5 mol/  96^(b) DCM, rt FL 3 h 17 c-C₆H₁₁CO₂H DBI 1 mol/[NBu₄]Br₃ 0.5 mol/  80^(b) DCM, rt FL 3 h 18 c-C₅H₁₁CH(CO₂H)₂ DBI 2 mol/[NBu₄]Br₃ 1 mol/ 25 DCM, rt FL 3 h (55^(b)) 19 H(CH₂)₁₀CHBrCO₂H DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ 60 DCM, rt FL 3 h 20 PhCHClCO₂H DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ 80 DCM, rt FL 3 h 21 H(CH₂)₆CHClCO₂H DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ 68 DCM, rt FL 3 h 22 EtO₂C(CH₂)₄CHClCO₂H DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ 70 DCM, rt FL 3 h 23 PhCHFCO₂H DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ 73 DCM, rt FL 3 h 24 H(CH₂)₁₂CHFCO₂H DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ 76 DCM, rt FL 3 h 25 EtO₂C(CH₂)₄)CHFCO₂H DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ 64 DCM, rt FL 3 h 26 H(CH₂)₄CF(CO₂Et)CO₂H DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ 73 DCM, rt FL 4 h 27

DBI 1 mol/[NBu₄]Br₃ 0.3 mol/ DCM, rt FL 4 h 68 28

DBI 1 mol/Br₂ 0.3 mol/DCM, rt FL 4 h 61 29

DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ DCM, rt FL 4 h 80 30

DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ DCM, rt FL 2 h 52 31

DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ DCM, rt FL 3 h  60^(c) 32

DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ DCM, rt FL 3 h  90^(d) 33

DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ DCM, rt FL 4 h 38 34

DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ DCM, rt FL 4 h 86 35

DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ DCM, rt FL 4 h 90 36

DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ DCM, rt FL 4 h 72 37

DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ DCM, rt FL 3 h 26 38

DBI 1 mol/[NBu₄]Br₃ 0.3 mol/ DCM, rt FL 4 h 76 39

DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ DCM, rt FL 3 h 26 40

DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ DCM, rt FL 3 h 82 41 CH₂BrCHBr(CH₂)₅CO₂H DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ 77 DCM, rt FL 4 h 42

DBI 1 mol/[NBu₄]Br₃ 0.5 mol/ DCM, rt FL 3 h 67 ^(a) All quantities in mole/mole of alkanoic acid. ^(b)Yield determined by GC. ^(c)Mixture of 1.4:1 trans/cis bromides (¹H NMR) ^(d)Mixture of 2:1 exo/endo bromides (¹H NMR)

Entry 1: 1-Bromoundecane ¹H NMR: δ 3.38 (t, J=7 Hz, 2H), 1.84 (m, 2H), 1.40 (m, 2H), 1.27 (s, 14H), 0.87 (t, J=7 Hz, 3H) ppm; ¹³C NMR: δ 33.9, 33.0, 32.0, 29.71, 29.69, 29.59, 29.5, 28.9, 28.3, 22.8, 14.2 ppm.

Entry 3: (2-Bromoethyl)cyclohexane ¹H NMR: δ 3.24 (t, J=7 Hz, 2H), 1.61-1.79 (m, 7H), 1.40-1.52 (m, 3H), 0.85-0.98 (m, 2H) ppm; ¹³C NMR: δ 40.4, 36.3, 32.7, 31.8, 26.5, 26.1 ppm.

Entry 4: 1,10-Dibromodecane ¹H NMR: δ 3.39 (t, J=7 Hz, 4H), 1.84 (m, 4H), 1.41 (m, 4H), 1.29 (s, 8H) ppm; ¹³C NMR: δ 34.0, 32.8, 29.3, 28.7, 28.1 ppm.

Entry 5: Methyl 7-bromoheptanoate ¹H NMR: δ 3.66 (s, 3H), 3.40 (t, J=7 Hz, 2H), 2.31 (t, J=7 Hz, 2H), 1.86 (m, 2H), 1.64 (m, 2H), 1.45 (m, 2H), 1.37 (m, 2H) ppm; ¹³C NMR: δ 173.9, 51.4, 33.8, 33.7, 32.5, 28.2, 27.7, 24.6 ppm.

Entry 6: 3-Bromo-1-(4-chlorophenyl)propan-1-one ¹H NMR: δ 7.89 (d, J=9 Hz, 2H), 7.44 (d, J=9 Hz, 2H), 3.73 (t, J=7 Hz, 2H), 3.55 (t, J=7 Hz, 2H) ppm; ¹³C NMR: δ 195.7, 139.9, 134.5, 129.4, 129.0, 41.4, 25.6 ppm.

Entry 7: 4-Bromo-1-phenylbutan-1-one ¹H NMR: δ 7.99 (d, J=4 Hz, 2H), 7.58 (t, J=7 Hz, 1H), 7.48 (t, J=8 Hz, 2H), 3.56 (t, J=6 Hz, 2H), 3.18 (t, J=7 Hz, 2H), 2.30 (quint, J=7 Hz, 2H) ppm; ¹³C NMR: δ 198.5, 136.6, 133.1, 128.5, 127.9, 36.4, 33.6, 26.8 ppm.

Entry 8: 5-Bromo-1-phenylpentan-1-one ¹H NMR: δ 7.95 (d, J=7 Hz, 2H), 7.56 (t, J=7 Hz, 1H), 7.46 (t, J=7 Hz, 2H), 3.45 (t, J=7 Hz, 2H), 3.01 (t, J=7 Hz, 2H), 1.87-2.0 (m, 4H) ppm; ¹³C NMR: δ 199.7, 136.9, 133.2, 128.7, 128.1, 37.5, 33.4, 32.3, 22.9 ppm.

Entry 9: Benzyl bromide ¹H NMR: δ 7.46-7.59 (m, 5H), 4.45 (s, 2H) ppm; ¹³C NMR δ 137.7, 128.9, 128.6, 128.3, 33.6 ppm.

Entry 10: 4-Chlorobenzyl bromide ¹H NMR: δ 7.33 (s, 4H), 4.47 (s, 2H) ppm; ¹³C NMR: δ 136.3, 134.3, 130.4, 129.0, 32.5 ppm.

Entry 11: 4-Bromomethylbiphenyl ¹H NMR: δ 7.54-7.61 (m, 4H), 7.41-7.48 (m, 4H), 7.34-7.39 (m, 1H), 4.52 (s, 2H) ppm; ¹³C NMR: δ 141.3, 140.4, 136.8, 129.5, 128.8, 127.6, 127.5, 127.1, 33.5 ppm.

Entry 12: (1-Bromoethyl)benzene ¹H NMR: δ 7.27-7.46 (m, 5H), 5.22 (q, J=7 Hz, 1H), 2.05 (d, J=7 Hz, 3H) ppm; ¹³C NMR: δ 143.3, 128.7, 128.4, 126.9, 49.6, 26.9 ppm.

Entry 14: 2-Bromooctadecane ¹H NMR: δ 4.12 (m, 1H), 1.75-1.89 (m, 2H), 1.71 (d, J=7 Hz, 2H), 1.40-1.58 (m, 3H), 1.28 (m, 26H), 0.9 (t, J=7 Hz, 3H) ppm; ¹³C NMR: δ 51.5, 41.4, 32.1, 29.88, 29.85, 29.82, 29.76, 29.67, 29.55, 29.2, 27.9, 26.6, 22.8, 14.2 ppm.

Entry 15: Ethyl 2-bromo-2-ethylbutyrate ¹H NMR: 4.21 (q, J=7 Hz, 2H), 2.09 (m, 4H), 1.27 (t, J=7 Hz, 3H), 0.95 (t, J=7 Hz, 6H) ppm; ¹³C NMR 170.9, 70.1, 62.0, 32.7, 14.1, 10.1 ppm.

Entry 18: (Dibromomethyl)cyclopentane ¹H NMR: δ 5.70 (d, J=6 Hz, 2H), 2.60-2.77 (m, 1H), 1.86-1.96 (m, 2H), 1.40-1.78 (6H) ppm; ¹³C NMR: δ 52.6, 52.5, 31.6, 26.0 ppm.

Entry 19: 1,1-Dibromoundecane ¹H NMR: δ 5.7 (t, J=6 Hz, 1H), 2.39 (m, 2H), 1.48-1.58 (m, 2H), 1.27 (m, 14H), 0.88 (t, J=7 Hz, 3H) ppm; ¹³C NMR: δ 46.4, 45.6, 32.0, 29.7, 29.6, 29.5, 29.5, 28.4, 28.2, 22.8, 14.2 ppm.

Entry 20: (Bromochloromethyl)benzene ¹H NMR: δ 7.56-7.63 (m, 2H), 7.33-7.45 (m, 3H), 6.76 (s, 1H) ppm; ¹³C NMR: δ 141.3, 130.0, 128.8, 126.3, 57.6 ppm.

Entry 21: 1-Bromo-1-chloroheptane ¹H NMR: δ 5.76 (t, 1H, J=6 Hz, 1H), 2.28 (m, 2H), 1.53 (m, 2H), 1.3 (m, 7H), 0.89 (t, J=7 Hz, 3H) ppm; ¹³C NMR: δ 61.1, 44.8, 31.2, 28.2, 27.1, 22.6, 14.1 ppm.

Entry 22: Ethyl 6-bromo-6-chlorohexanoate ¹H NMR: 5.75 (t, J=6 Hz, 1H), 4.09 (q, J=7 Hz, 2H), 2.24-2.33 (m, 4H), 1.60-1.70 (m, 2H), 1.51-1.60 (m, 2H), 1.20 (t, J=7 Hz, 3H) ppm; ¹³C NMR 173.2, 60.5, 60.4, 53.5, 44.2, 34.0, 26.5, 23.8, 14.3 ppm.

Entry 23: (Bromofluoromethyl)benzene ¹H NMR: δ 7.33-7.55 (m, 6H) ppm; 13C NMR: δ 138.8 (d, J_(CF)=20 Hz), 130.3, 128.8, 125.2 (d, J_(CF)=6 Hz), 92.2 (d, J_(CF)=254 Hz) ppm; ¹⁹F NMR: δ −133.3 ppm.

Entry 24: 1-Bromo-1-fluorotridecane ¹H NMR: δ 6.45 (dt, J=51, 5 Hz, 1H), 2.07-2.29 (m, 2H), 1.46-1.56 (m, 2H), 1.27 (m, 19H), 0.88 (t, J=7 Hz, 3H) ppm; ¹³C NMR: δ 95.9 (d, J_(CF)=252 Hz), 40.8 (d, J_(CF)=19 Hz), 32.0, 29.79, 29.78, 29.73, 29.6, 29.5, 28.8, 25.22, 25.18, 22.8, 14.1 ppm; ¹⁹F NMR: −133.3 ppm.

Entry 25: Ethyl 6-bromo-6-fluorohexanoate ¹H NMR: 6.42 (dt, J=50, 5.4 Hz, 1H), 4.10 (q, J=7 Hz, 2H), 2.28 (t, J=7 Hz, 2H), 2.00-2.23 (m, 2H), 1.60-1.69 (m, 2H), 1.56-1.60 (m, 2H), 1.20 (t, J=7 Hz, 3H) ppm; ¹³C NMR 173.2, 95.2 (d, J_(CF)=252 Hz), 60.4, 40.2 (d, J_(CF)=19 Hz), 34.0, 24.6 (d, J_(CF)=4 Hz), 24.0, 14.3 ppm; ¹⁹F NMR: δ −134.0 ppm.

Entry 26: Ethyl 2-bromo-2-fluorohexanoate ¹H NMR: 4.34 (q, J=7 Hz, 2H), 2.30-2.50 (m, 2H), 1.50-1.65 (2H), 1.31-1.45 (m, 6H), 0.93 (t, J=7 Hz, 3H) ppm; ¹³C NMR 166.3 (d, J_(CF)=27 Hz), 98.7 (d, J_(CF)=266 Hz), 63.1, 41.4, (d, J_(CF)=21 Hz), 26.4 (d, J_(CF)=1.4 Hz), 22.1, 13.9, 13.8 ppm; ¹⁹F NMR: δ −120.1 ppm.

Entry 27: 3α, 7α, 12α-Triformyloxy-5β-23-bromo-24-nor-cholane ¹H NMR: δ 8.15 (s, 1H), 8.02 (s, 1H), 8.01 (s, 1H), 5.27 (m, 1H), 5.07 (m, 1H), 4.70 (m, 1H), 3.43-3.35 (m, 1H), 3.27-3.38 (m, 1H), 1.02-2.18 (m, 25H), 0.94 (s, 3H), 0.85 (d, J=6 Hz, 3H), 0.77 (s, 3H) ppm; ¹³C NMR: δ 160.69, 160.68, 160.6, 75.4, 73.9, 70.8, 47.5, 45.3, 43.1, 40.9, 39.0, 37.8, 34.6, 34.6, 34.5, 34.4, 34.4, 31.8, 31.5, 28.7, 27.4, 26.7, 25.7, 22.9 ppm.

Entry 28: N-(5-Bromopentyl)phthalimide ¹H NMR: δ 7.80 (dd, J=5, 3 Hz, 2H), 7.70 (dd, J=5, 3 Hz, 2H), 3.68 (t, J=7 Hz, 2H), 3.38 (t, J=7 Hz, 2H), 1.89 (m, 2H), 1.70 (m, 2H), 1.49 (m, 2H) ppm; ¹³C NMR: δ 168.3, 133.9, 132.0, 37.6, 33.4, 32.2, 27.7, 25.3 ppm.

Entry 29: Ethyl 1-bromocyclobutanoate ¹H NMR: δ 4.19 (q, J=7 Hz, 2H), 2.80-2.90 (m, 2H), 2.50-2.60 (m, 2H), 2.10-2.20 (m, 1H), 1.76-1.87 (m, 1H), 1.25 (t, J=7 Hz, 3H) ppm; ¹³C NMR: δ 171.5, 61.9, 54.3, 37.2, 16.7, 13.9 ppm.

Entry 30: Methyl 4-bromocubanecarboxylate ¹H NMR: δ 4.22-4.35 (m, 6H), 3.70 (s, 3H) ppm; ¹³C NMR: δ 172.0, 63.3, 56.4, 54.7, 51.8, 47.9 ppm.

Entry 31: trans-1-Bromo-2-(4-chlorobenzoyl)cyclohexane ¹H NMR: δ 7.93 (d, J=9 Hz, 2H), 7.46 (d, J=9 Hz, 2H), 4.41 (m, 1H), 3.76 (m, 1H), 2.49 (m, 1H), 1.91-2.00 (m, 2H), 1.79-1.89 (m, 2H), 1.37-1.50 (m, 3H) ppm; ¹³C NMR: δ 200.0, 140.0, 134.7, 130.0, 129.2, 54.1, 51.4, 37.5, 31.9, 27.0, 24.9 ppm.

Entry 32: endo-2-Bromonorbornane ¹H NMR: δ 4.27-4.33 (m, 1H) ppm; ¹³C NMR: δ 54.1, 43.5, 41.6, 37.7, 37.17, 29.6, 24.5 ppm.

Entry 32: exo-2-Bromonorbornane ¹H NMR: δ 3.96-4.02 (m, 1H) ppm; ¹³C NMR: δ 54.1, 46.6, 44.0, 37.2, 35.6, 28.2, 27.7 ppm.

Entry 33: (1S)-1-Bromoapocamphan-2-one ¹H NMR: δ 2.52 (m, 1H), 1.93-2.27 (m, 5H), 1.50 (m, 1H), 1.08 (s, 3H), 0.95 (s, 3H) ppm; ¹³C NMR: δ 209.0, 77.1, 49.1, 42.5, 40.7, 32.8, 28.1, 20.1, 19.6 ppm.

Entry 34: 1-(Bromomethyl)adamantine ¹H NMR: δ 3.13 (s, 2H), 1.98 (m, 3H), 1.69 (d, J=12 Hz, 3H), 1.62 (d, J=12 Hz, 3H), 1.54 (m, 6H) ppm; ¹³C NMR: δ 48.4, 40.7, 36.8, 33.6, 28.5 ppm.

Entry 35: 1-Bromoadamantane ¹H NMR: δ 2.37 (d, J=3 Hz, 6H), 2.1 (m, 3H), 1.73 (m, 6H) ppm; ¹³C NMR: δ 49.4, 35.6, 32.6 ppm.

Entry 36: 3-Bromonoradamantane ¹H NMR: δ 2.65 (t, J=7 Hz, 1H), 2.16-2.30 (m, 6H), 1.95-2.05 (m, 2H), 1.43-1.63 (m, 4H) ppm; ¹³C NMR: δ 66.1, 55.4, 48.8, 43.4, 38.5, 33.4 ppm.

Entry 37: 1-Boc-3-bromoazetidine ¹H NMR: δ 4.49 (m, 3H), 4.16 (m, 2H), 1.42 (s, 9H) ppm; ¹³C NMR: δ 155.8, 80.3, 60.3, 33.0, 28.4 ppm.

Entry 38: 1-Boc-4-(bromomethyl)piperidine ¹H NMR: δ 4.13 (m, 1H), 3.29 (d, J=6 Hz, 2H), 2.69 (m, 2H), 1.78-1.85 (m, 3H), 1.46 (s, 9H), 1.10-1.23 (m, 2H) ppm; ¹³C NMR: δ 154.8, 79.5, 43.6, 38.9, 38.7, 30.9, 28.5 ppm.

Entry 39: 1-Boc-4-bromopiperidine ¹H NMR: δ 4.30 (m, 1H), 3.60-3.70 (m, 2H), 3.24-3.32 (m, 2H), 2.00-2.10 (m, 2H), 1.85-1.95 (m, 2H), 1.43 (s, 9H) ppm; ¹³C NMR: δ 154.7, 79.9, 49.6, 42.2 (bs), 35.7, 28.5 ppm.

Entry 40: 4-Bromo-1-(methylsulfonyl)piperidine ¹H NMR: δ 4.43 (m, 1H), 3.37 (m, 4H), 2.80 (s, 3H), 2.16-2.28 (m, 2H), 2.05-2.14 (m, 2H) ppm; ¹³C NMR: δ 48.2, 43.2, 35.0, 34.7 ppm.

Entry 41: 1,2,7-Tribromoheptane ¹H NMR: δ 4.17 (m, 1H), 3.86 (dd, J=10, 4 Hz, 1H), 3.62 (t, J=10 Hz, 1H), 3.42 (t, J=7 Hz, 1H), 2.11-2.21 (m, 1H), 1.75-1.94 (m, 3H), 1.41-1.67 (m, 5H) ppm; ¹³C: δ 52.8, 36.3, 35.9, 33.7, 32.6, 27.5, 26.1 ppm.

Entry 42: N-(6-Bromo-6-fluorohexyl)phthalimide ¹H NMR: δ 7.83-7.86 (m, 2H), 7.70-7.73 (m, 2H), 6.44 (dt, J=50, 5 Hz, 1H), 3.70 (t, 2H), 2.08-2.28 (m, 2H), 1.71 (m, 2H), 1.51-1.61 (m, 3H), 1.36-1.46 (m, 2H) ppm; ¹³C NMR: δ 168.4, 133.9, 132.1, 123.1, 95.4 (d, J_(CF)=252 Hz), 40.7 (d, J_(CF)=41 Hz), 37.7, 28.3, 25.9, 24.6, 24.56 ppm; ¹⁹F NMR: δ −133.8 ppm.

Example 13 Bromodecarboxylation of Lauric Acid: Solvent Selection

A mixture of lauric acid (0.5 mmol), DBI (0.5 mmol), [NBu₄]Br₃ (0.15 mmol), and solvent (4 mL) was stirred under fluorescent room light irradiation (FL) or warm-white 3 W LED lamp irradiation (LL). An aliquot of the reaction mixture washed with 1 M aq Na₂SO₃, dried over Na₂SO₄, and filtered through short neutral silica gel pad. The yield of 1-bromoundecane was determined by gas chromatography (GC) using 1,2,4,5-tetrachlorobenzene as internal standard. The results are presented in Table 12.

TABLE 12 Bromodecarboxylation of lauric acid ^(a) entry Reaction conditions yield, % ^(b) 1 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 4 h 98 2 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCE, rt FL 4 h 55 3 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/CHCl₃, rt FL 4 h 73 4 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/CCl₄, rt FL 4 h 6 5 DBI 1 mol/Br₂ 1 mol/DCM, rt FL 1 h 43 6 DBI 1 mol/Br₂ 1 mol/DCM, rt FL 2 h 73 7 DBI 1 mol/Br₂ 1 mol/DCM, rt FL 3 h 70 8 DBI 1 mol/Br₂ 1 mol/DCM, rt FL 4 h 60 9 DBI 1 mol/Br₂ 1 mol/CCl₄, rt FL 1 h 11 10 DBI 1 mol/Br₂ 1 mol/CCl₄, rt FL 2 h 27 11 DBI 1 mol/Br₂ 1 mol/CCl₄, rt FL 18 h 20 12 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/C₆H₆, rt FL 4 h 77 13 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/PhCl, rt FL 4 h 73 14 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/MeCN, rt FL 4 h 29 15 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/MeOAc, rt LL 1 h 44 16 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/MeOAc, rt LL 2 h 53 17 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/MeOAc, rt LL 3 h 53 18 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/EtOAc, rt LL 1 h 60 19 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/EtOAc, rt LL 2 h 68 20 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/EtOAc, rt LL 4 h 68 ^(a) All quantities in mole/mole of lauric acid. ^(b) 1-Bromoundecane analyzed by GC.

Example 14 Bromodecarboxylation of Lauric Acid: N-Bromoamide Selection

A mixture of lauric acid (0.5 mmol), N-bromoamide (0.5 mmol), [NBu₄]Br₃ (0.15 mmol), and DCM (4 mL) was stirred under fluorescent room light irradiation (FL) or warm-white 3 W LED lamp irradiation (LL). An aliquot of the reaction mixture washed with 1 M aq Na₂SO₃, dried over Na₂SO₄, and filtered through short neutral silica gel pad. The yield of 1-bromoundecane was determined by gas chromatography (GC) using 1,2,4,5-tetrachlorobenzene as internal standard. The results are presented in Table 13.

TABLE 13 N-Bromoamides as reagents for radical bromodecarboxylation ^(a) entry Reaction conditions yield, % ^(b) DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 4 h 98 DBI 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 20 h 71 NBS 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 4 h 1 NBS 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 20 h 2 NBSsac 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 4 h 1 DBDMH 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 4 h 4 DBDMH 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 20 h 10 BTH 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 4 h 2 BTH 1 mol/[NBu₄]Br₃ 0.3 mol/DCM, rt FL 20 h 5 ^(a) All quantities in mole/mole of lauric acid. ^(b) 1-Bromoundecane analyzed by GC.

Example 15 Bromodecarboxylation of Lauric Acid: Recovery of Onium Compound

A mixture of lauric acid (3.13 g, 15.7 mmol), dibromoisocyanuric acid DBI (4.50 g, 15.7 mmol), tetrapropylammonium tribromide [NPr₄]Br₃ (2.00 g, 4.7 mmol) and DCM (45 mL) was stirred under warm-white 3 W LED lamp irradiation (LL) for 7 h at 0° C. The mixture was filtered and the filtrate was washed with 1M aq Na₂SO₃ (6.3 mL, 6.3 mmol) and water (20 mL), dried over Na₂SO₄, filtered and concentrated in vacuo to give 1-bromoundecane (3.56 g, 97% yield).

The combined aqueous phases were treated with Br₂ (1.01 g, 6.3 mmol), washed with DCM (2×60 mL). DCM fraction was dried over Na₂SO₄, filtered and concentrated in vacuo giving g (1.36 g, 68% recovery) of [NPr₄]Br₃.

Example 16 Bromodecarboxylation of Lauric Acid with Bromoisocyanurate

A: Preparation of Bromoisocyanurate

The mixture of trichloroisocyanuric acid TCCA (10.0 g, 43.1 mmol), Br₂ (41.9 g, 262 mmol) and DCM (50 mL) was stirred at rt in the dark for 18 h. The precipitate was filtered off, washed on the filter with DCM and treated with Br₂ (41.9 g, 262 mmol) in DCM (50 mL) at rt in the dark for 18 h. The precipitate was filtered off, washed on the filter with DCM and dried in vacuo giving 14.1 g of bromoisocyanurate.

B: Bromodecarboxylation of Lauric Acid with Bromoisocyanurate

A mixture of lauric acid (0.28 g, 1.4 mmol), bromoisocyanurate from step A (0.39 g), tetrapropylammonium tribromide [NPr₄]Br₃ (0.58 g, 1.4 mmol), and DCM (4 mL) was stirred at 0° C. under 3 W warm-white LED lamp irradiation (LL) for 5 h. The mixture was washed with 1 M aq Na₂SO₃, dried over Na₂SO₄, filtered and concentrated in vacuo. The residue was purified by chromatography on silica to yield 0.30 g (90%) of 1-bromoundecane.

While certain features of the invention have been illustrated and described herein, many modifications, substitutions, changes, and equivalents will now occur to those of ordinary skill in the art. It is, therefore, to be understood that the appended claims are intended to cover all such modifications and changes as fall within the true spirit of the invention. 

What is claimed is:
 1. A process for the preparation of organic bromide of formula (1A) from a carboxylic acid of formula (2A) represented by scheme 1:

said process comprises radical bromodecarboxylation reaction of carboxylic acid (2A) with a bromoisocyanurate to yield organic bromide (1A); wherein said bromoisocyanurate is tribromoisocyanuric acid, dibromoisocyanuric acid, bromodichloroisocyanuric acid, dibromochloroisocyanuric acid, bromochloroisocyanuric acid, or any combination thereof; A is arene, alkane, cycloalkane or saturated heterocycle; n is an integer of at least 1; m is an integer of at least 0; and each Q is independently F, Cl, Br, R¹, acyl, C(O)R¹, C(O)OR¹, C(O)Cl, C(O)N(R¹)₂, CN, SO₂R¹, SO₃R¹, NO₂, N(R¹)₃ ⁺, OR¹, OCF₃, O-acyl, OC(O)R¹, OSO₂R¹, SR¹, S-acyl, SC(O)R¹, N(R¹)acyl, N(R¹)C(O)R¹, N(R¹)SO₂R¹, N(acyl)₂, N[C(O)R¹]SO₂R¹, N[C(O)R¹]₂, CF₃; or any two vicinal Q substituents are joined to form a 5- or 6-membered substituted or unsubstituted, saturated or unsaturated carbocyclic or heterocyclic ring; wherein each R¹ is independently aryl, alkyl, cycloalkyl or heterocyclyl, wherein said R¹ is optionally substituted by one or more substituents of R²; wherein each R² is independently F, Cl, Br, COOH, acyl, aryl, alkyl, cycloalkyl or heterocyclyl; wherein if either one of R² in (2A) is carboxylic group COOH, then the respective R² in (1A) is Br; wherein the position of said Br and Q in said structure of formula (1A) correspond to the same position of said COOH and Q, respectively in said structure of formula (2A).
 2. The process of claim 1, wherein A is benzene.
 3. The process of claim 1, wherein said organic bromide is bromoarene of formula (1B):

and said carboxylic acid is arenecarboxylic acid of formula (2B)

wherein Q¹, Q², Q³, Q⁴, and Q⁵, are each independently selected from: H, F, Cl, Br, R¹, COOH, acyl, C(O)R¹, acetyl, benzoyl, C(O)OR¹, C(O)Cl, C(O)N(R¹)₂, CN, SO₂R¹, SO₃R¹, NO₂, N(R¹)₃ ⁺, OR¹, OCF₃, O-acyl, OC(O)R¹, OSO₂R¹, SR¹, S-acyl, SC(O)R¹, N(R¹)acyl, N(R¹)C(O)R², N(R¹)SO₂R¹, N(acyl)₂, N[C(O)R¹]SO₂R¹, N[C(O)R¹]₂, CF₃; or any two of Q¹ and Q², Q² and Q³, Q³ and Q⁴, or Q⁴ and Q⁵, are joined to form a 5- or 6-membered substituted or unsubstituted, saturated or unsaturated carbocyclic or heterocyclic ring; wherein each R¹ is independently aryl, alkyl, cycloalkyl or heterocyclyl; wherein R¹ is optionally substituted by one or more substituents of R²; wherein each R² is independently F, Cl, Br, COOH, acyl, aryl, alkyl, cycloalkyl or heterocyclyl; wherein if either one of Q¹, Q², Q³, Q⁴, Q⁵, and/or R² in (2B) is carboxylic group COOH, then the respective Q¹, Q², Q³, Q⁴, Q⁵, and/or R² in (1B) is Br.
 4. The process of claim 3, wherein at least one of Q¹, Q², Q³, Q⁴, and/or Q⁵ is F, Cl, Br, CF₃, CCl₃, CN, COOH, C(O)OMe, NO₂, OCF₃, and/or any two of Q¹ and Q², Q² and Q³, Q³ and Q⁴, or Q⁴ and Q⁵, are joined to form a dihydrofuran-2,5-dione or pyrrolidine-2,5-dione ring.
 5. The process of claim 1, wherein the molar ratio of bromoisocyanurate/(each carboxylic group of the carboxylic acid of formula (2A)) is between 0.1 and
 2. 6. The process of claim 1, wherein said bromodecarboxylation reaction further comprises an additive.
 7. The process of claim 6, wherein said additive is Br₂ (bromine), a salt comprising bromide or polybromide anion and organic or inorganic cation; or any combination thereof.
 8. The process of claim 7, wherein said polybromide anion is an ion of formula [Br_(p)]^(q−) where p is an integer of at least 3 and q is an integer of at least 1 and not more than p/2.
 9. The process of claim 7, wherein said cation is substituted or unsubstituted onium ion.
 10. The process of claim 9, wherein said onium ion comprises substituted or unsubstituted ammonium, oxonium, phosphonium, sulfonium, arsonium, selenonium, telluronium, iodonium ion or any combination thereof.
 11. The process of claim 10, wherein said ammonium ion is tertiary or quaternary ammonium, substituted or unsubstituted pyridinium, amidinium or guanidinium ion; or any combination thereof; or said phosphonium ion is quaternary phosphonium ion; or said sulfonium ion is tertiary sulfonium, substituted; or unsubstituted sulfoxonium, thiopyrylium or thiuronium ion; or any combination thereof; or said oxonium ion is tertiary oxonium, substituted or unsubstituted pyrylium ion; or any combination thereof.
 12. The process of claim 6, wherein the molar ratio of the additive/(each carboxylic group of the carboxylic acid of formula (2A)) is between 0.1 and
 4. 13. The process of claim 1, wherein said bromodecarboxylation reaction further comprises an organic or inorganic solvent or combination thereof.
 14. The process of claim 13, wherein said organic solvent is CH₃CN, CH₃NO₂, ester, a hydrocarbon solvent, or halocarbon solvent or combination thereof.
 15. The process of claim 14, wherein said hydrocarbon solvent is C₆H₆; and said halocarbon solvent is CH₂Cl₂, Cl(CH₂)₂Cl, CHCl₃, CCl₄, C₆H₅Cl, o-C₆H₄Cl₂, BrCCl₃, CH₂Br₂, CFCl₃, CF₃CCl₃, ClCF₂CFCl₂, BrCF₂CFClBr, CF₃CClBr₂, CF₃CHBrCl, C₆H₅F, C₆H₅CF₃, 4-ClC₆H₄CF₃, 2,4-Cl₂C₆H₃CF₃, or any combination thereof.
 16. The process of claim 1, wherein in order to accelerate the radical bromodecarboxylation reaction the reaction mixture is subjected to electromagnetic irradiation.
 17. The process of claim 1, wherein said bromodecarboxylation reaction further comprises a radical initiator.
 18. The process of claim 17, wherein said radical initiator is an azo compound or organic peroxide.
 19. The process of claim 18, wherein said azo compound is azobisisobutyronitrile (AIBN) or 1,1′-azobis(cyclohexanecarbonitrile) (ABCN).
 20. The process of claim 18, wherein said organic peroxide is benzoyl peroxide.
 21. A radiation-sensitive composition comprising carboxylic acid of formula (2A)

and bromoisocyanurate which generates organic bromide of formula (1A)

upon electromagnetic irradiation, wherein the bromoisocyanurate is tribromoisocyanuric acid, dibromoisocyanuric acid, bromodichloroisocyanuric acid, dibromochloroisocyanuric acid, bromochloroisocyanuric acid, or any combination thereof; A is arene, alkane, cycloalkane or saturated heterocycle; n is an integer of at least 1; m is an integer of at least 0; each Q is independently F, Cl, Br, R¹, acyl, C(O)R¹, C(O)OR¹, C(O)OMe, C(O)Cl, C(O)N(R¹)₂, CN, SO₂R¹, SO₃R¹, NO₂, N(R¹)₃ ⁺, OR¹, OCF₃, O-acyl, OC(O)R¹, OSO₂R¹, SR¹, S-acyl, SC(O)R¹, N(R¹)acyl, N(R¹)C(O)R¹, N(R¹)SO₂R¹, N(acyl)₂, N[C(O)R¹]SO₂R¹, N[C(O)R¹]₂, CF₃; or any two vicinal Q substituents are joined to form a 5- or 6-membered substituted or unsubstituted, saturated or unsaturated carbocyclic or heterocyclic ring; wherein each R¹ is independently aryl, alkyl, cycloalkyl or heterocyclyl, wherein R¹ is optionally substituted by one or more substituents of R²; wherein each R² is independently F, Cl, Br, COOH, acyl, aryl, alkyl, cycloalkyl or heterocyclyl; wherein if either one of R² in (2A) is a carboxylic group COOH, then the respective R² in (1A) is Br; wherein the position of said Br and Q in said structure of formula (1A) correspond to the same position of said COOH and Q, respectively in said structure of formula (2A).
 22. The composition of claim 21, wherein A is benzene.
 23. The composition of claim 21, wherein said carboxylic acid is arenecarboxylic acid of formula (2B)

and said organic bromide is bromoarene of formula (1B)

wherein Q¹, Q², Q³, Q⁴, and Q⁵, are each independently selected from: H, F, Cl, Br, R¹, COOH, acyl, C(O)R¹, C(O)OR¹, C(O)Cl, C(O)N(R¹)₂, CN, SO₂R¹, SO₃R¹, NO₂, N(R¹)₃ ⁺, OR¹, OCF₃, O-acyl, OC(O)R¹, OSO₂R¹, SR¹, S-acyl, SC(O)R¹, N(R¹)acyl, N(R¹)C(O)R², N(R¹)SO₂R¹, N(acyl)₂, N[C(O)R¹]SO₂R¹, N[C(O)R¹]₂, CF₃; or any two of Q¹ and Q², Q² and Q³, Q³ and Q⁴, or Q⁴ and Q⁵, are joined to form a 5- or 6-membered substituted or unsubstituted, saturated or unsaturated carbocyclic or heterocyclic ring; wherein each R¹ is independently aryl, alkyl, cycloalkyl or heterocyclyl wherein R¹ is optionally substituted by one or more substituents of R²; wherein each R² is independently F, Cl, Br, COOH, acyl, aryl, alkyl, cycloalkyl or heterocyclyl; wherein if either one of Q¹, Q², Q³, Q⁴, Q⁵, and/or R² in (2B) is carboxylic group COOH, then the respective Q¹, Q², Q³, Q⁴, Q⁵, and/or R² in (1B) is Br.
 24. The composition of claim 23, wherein at least one of Q², Q³, Q, Q⁴, and/or Q⁵ is F, Cl, Br, CF₃, CCl₃, CN, COOH, C(O)OMe, NO₂, OCF₃, and/or any two of Q¹ and Q², Q² and Q³, Q³ and Q⁴, or Q⁴ and Q⁵, are joined to form a dihydrofuran-2,5-dione or pyrrolidine-2,5-dione ring.
 25. The composition of claim 21, wherein the molar ratio of bromoisocyanurate/(each carboxylic group of the carboxylic acid of formula (2A)) is between 0.1 and
 2. 26. The composition of claim 21, which further comprises an additive.
 27. The composition of claim 26, wherein said additive is Br₂ (bromine), a salt containing bromide or polybromide anion and organic or inorganic cation; or any combination thereof.
 28. The composition of claim 27, wherein said polybromide anion is an ion of formula [Br_(p)]^(q−) where p is an integer of at least 3 and q is an integer of at least 1 and no more than p/2.
 29. The composition of claim 27, wherein said cation is substituted or unsubstituted onium ion.
 30. The composition of claim 29, wherein said onium ion comprises substituted or unsubstituted ammonium, oxonium, phosphonium, sulfonium, arsonium, selenonium, telluronium, iodonium ion or any combination thereof.
 31. The composition of claim 30, wherein said ammonium ion is tertiary or quaternary ammonium, substituted or unsubstituted pyridinium, amidinium or guanidinium ion; or any combination thereof; or wherein said phosphonium ion is quaternary phosphonium ion; or wherein said sulfonium ion is tertiary sulfonium, substituted or unsubstituted sulfoxonium, thiopyrylium or thiuronium ion; or any combination thereof; or wherein said oxonium ion is tertiary oxonium, substituted or unsubstituted pyrylium ion.
 32. The composition of claim 31, wherein said quaternary ammonium is tetraalkylammonium, trialkylarylammonium, or trialkylbenzylammonium.
 33. The composition of claim 26, wherein the molar ratio of the additive/(each carboxylic group of the carboxylic acid of formula (2A)) is between 0.1 and
 4. 34. The composition of claim 21, which further comprises of an organic or inorganic solvent or combination thereof.
 35. The composition of claim 34, wherein said organic solvent is CH₃CN, CH₃NO₂, ester, a hydrocarbon solvent, or halocarbon solvent or combination thereof.
 36. The composition of claim 35, wherein said hydrocarbon solvent is C₆H₆; and said halocarbon solvent is CH₂Cl₂, Cl(CH₂)₂Cl, CHCl₃, CCl₄, C₆H₅Cl, o-C₆H₄Cl₂, BrCCl₃, CH₂Br₂, CFCl₃, CF₃CCl₃, ClCF₂CFCl₂, BrCF₂CFClBr, CF₃CClBr₂, CF₃CHBrCl, C₆H₅F, C₆H₅CF₃, 4-ClC₆H₄CF₃, 2,4-Cl₂C₆H₃CF₃, or any combination thereof. 